| 1. |
- Carlsén, Stefan, et al.
(author)
-
Cartilage oligomeric matrix protein induction of chronic arthritis in mice
- 2008
-
In: Arthritis and Rheumatism. - : Wiley. - 0004-3591 .- 1529-0131. ; 58:7, s. 2000-2011
-
Journal article (peer-reviewed)abstract
- OBJECTIVE: To develop a new mouse model for arthritis using cartilage oligomeric matrix protein (COMP) and to study the role of major histocompatibility complex (MHC) and Ncf1 genes in COMP-induced arthritis (COMPIA). METHODS: Native (pentameric) and denatured (monomeric) COMP purified from a rat chondrosarcoma was injected into mice with Freund's adjuvant to induce arthritis. C3H.NB, C3H.Q, B10.P, B10.Q, (B10.Q x DBA/1)F1, (BALB/c x B10.Q)F1, Ncf1 mutated, H-2Aq, H-2Ap, and human DR4+-transgenic mice were used. Anti-COMP antibodies and COMP levels in the immune sera were analyzed, and passive transfer of arthritis with purified immune sera was tested. RESULTS: Immunization with rat COMP induced a severe, chronic, relapsing arthritis, with a female preponderance, in the mice. The disease developed in C3H.NB mice, but not in B10.P mice, although they share the same MHC haplotype. Both H-2q and H-2p MHC haplotypes allowed the initiation of COMPIA. Using H-2Aq-transgenic and H-2Ap-transgenic mice, we demonstrated a role of both the Aq and Ep class II molecules in this model. Interestingly, the introduction of a mutation in the Ncf1 gene, which is responsible for the reduced oxidative burst phenotype, into the COMPIA-resistant B10.Q mouse strain rendered them highly susceptible to arthritis. In addition, the transfer of anti-COMP serum was found to induce arthritis in naive mice. Mice transgenic for the rheumatoid arthritis (RA)-associated DR4 molecule were found to be highly susceptible to COMPIA. CONCLUSION: Using rat COMP, we have developed a new and unique mouse model of chronic arthritis that resembles RA. This model will be useful as an appropriate and alternative model for studying the pathogenesis of RA.
|
|
| 2. |
- Corthay, Alexandre, et al.
(author)
-
Collagen-induced arthritis development requires alpha beta T cells but not gamma delta T cells: studies with T cell-deficient (TCR mutant) mice
- 1999
-
In: International Immunology. - 1460-2377. ; 11:7, s. 1065-1073
-
Journal article (peer-reviewed)abstract
- Collagen type II (CII)-induced arthritis (CIA) in mice is a model for rheumatoid arthritis (RA) in which the role of T lymphocytes remains controversial. To clarify this, we have bred a targeted gene deletion of TCR beta or delta loci into two mouse strains susceptible to CIA, the B10.Q and DBA/1 strains. The TCRbeta-/- mice lacked alphabeta T cells, which was compensated by an expansion of B cells, gammadelta T cells and NK cells. The beta-/- mice, but not control beta+/- littermates, were completely resistant to CIA. The production of anti-CII IgG antibodies was also abolished in beta-/- mice, revealing a strict alphabeta T cell dependency. In contrast, beta-/- mice produced reduced, but significant, anti-CII IgM titers after immunization with either CII or ovalbumin, indicating a multispecificity for these alphabeta T cell-independent IgM antibodies. The TCRdelta-/- mice lacked gammadelta T cells but had no other significant changes in lymphocyte or monocyte subsets. The cytokine response (IL-2, IL-4, IL-10 and IFN-gamma) in delta-/- mice, quantified by flow cytometry staining of mitogen-stimulated lymphocytes, was indistinguishable from normal mice. Likewise, no statistically significant differences were observed in CIA between mice lacking gammadelta T cells and control littermates, considering arthritis incidence, day of disease onset, maximum arthritic score, anti-CII IgG titers and disease course. We conclude that alphabeta T cells are necessary for CIA development and for an IgG response towards CII, whereas gammadelta T cells are neither necessary nor sufficient for development of CIA.
|
|
| 3. |
- Dzhambazov, Balik, et al.
(author)
-
The major T cell epitope on type II collagen is glycosylated in normal cartilage but modified by arthritis in both rats and humans
- 2005
-
In: European Journal of Immunology. - : Wiley. - 1521-4141 .- 0014-2980. ; 35:2, s. 357-366
-
Journal article (peer-reviewed)abstract
- Type II collagen (CII) is a target for autoreactive T cells in both rheumatoid arthritis and the murine model collagen-induced arthritis. The determinant core of CII has been identified as CII260-270, and the alteration of this T cell epitope by posttranslational modifications is known to be critical for development of arthritis in mice. Using CII-specific T cell hybridomas we have now shown that the immunodominant T cell epitope in the normal (healthy) human and rat joint cartilage is O-glycosylated at the critical T cell receptor recognition position 264 with a mono- or di-saccharide attached to a hydroxylysine. In contrast, in the arthritic human and rat joint cartilage there are both glycosylated and non-glycosylated CII forms. Glycosylated CII from normal cartilage could not be recognized by T cells reactive to peptides having only lysine or hydroxylysine at position 264, showing that antigen-presenting cells could not degrade the O-linked carbohydrate. Thus, the variable forms of the glycosylated epitope are determined by the structures present in cartilage, and these vary during the disease course. We conclude that the chondrocyte determines the structures presented to the immune system and that these structures are different in normal versus arthritic states.
|
|
| 4. |
- Dzhambazov, Balik, et al.
(author)
-
The major T cell epitope on type II collagen is glycosylated in normal cartilage but modified by arthritis in both rats and humans
- 2005
-
In: EUROPEAN JOURNAL OF IMMUNOLOGY. - : Wiley. - 0014-2980 .- 1521-4141. ; 35:2, s. 357-66
-
Journal article (peer-reviewed)abstract
- Type II collagen (CII) is a target for autoreactive T cells in both rheumatoid arthritis and the murine model collagen-induced arthritis. The determinant core of CII has been identified as CII260-270, and the alteration of this T cell epitope by posttranslational modifications is known to be critical for development of arthritis in mice. Using CII-specific T cell hybridomas we have now shown that the immunodominant T cell epitope in the normal (healthy) human and rat joint cartilage is O-glycosylated at the critical T cell receptor recognition position 264 with a mono- or di-saccharide attached to a hydroxylysine. In contrast, in the arthritic human and rat joint cartilage there are both glycosylated and non-glycosylated CII forms. Glycosylated CII from normal cartilage could not be recognized by T cells reactive to peptides having only lysine or hydroxylysine at position 264, showing that antigen-presenting cells could not degrade the O-linked carbohydrate. Thus, the variable forms of the glycosylated epitope are determined by the structures present in cartilage, and these vary during the disease course. We conclude that the chondrocyte determines the structures presented to the immune system and that these structures are different in normal versus arthritic states.
|
|
| 5. |
- Dzhambazov, Balik, et al.
(author)
-
Therapeutic vaccination of active arthritis with a glycosylated collagen type II peptide in complex with MHC class II molecules
- 2006
-
In: Journal of Immunology. - Rockville, MD : American Association of Immunologists. - 0022-1767 .- 1550-6606. ; 176, s. 1525-33
-
Journal article (peer-reviewed)abstract
- In both collagen-induced arthritis (CIA) and rheumatoid arthritis, T cells recognize a galactosylated peptide from type II collagen (CII). In this study, we demonstrate that the CII259-273 peptide, galactosylated at lysine 264, in complex with Aq molecules prevented development of CIA in mice and ameliorated chronic relapsing disease. In contrast, nonglycosylated CII259-273/Aq complexes had no such effect. CIA dependent on other MHC class II molecules (Ar/Er) was also down-regulated, indicating a bystander vaccination effect. T cells could transfer the amelioration of CIA, showing that the protection is an active process. Thus, a complex between MHC class II molecules and a posttranslationally modified peptide offers a new possibility for treatment of chronically active autoimmune inflammation such as rheumatoid arthritis. © 2006 by The American Association of Immunologists, Inc.
|
|
| 6. |
- Ehinger, Magnus, et al.
(author)
-
Influence of CD4 or CD8 deficiency on collagen-induced arthritis
- 2001
-
In: Immunology. - : Wiley. - 0019-2805 .- 1365-2567. ; 103:3, s. 291-300
-
Journal article (peer-reviewed)abstract
- The role of T cells in the mouse collagen-induced arthritis (CIA) model for rheumatoid arthritis is not clarified, and different results have been reported concerning the role of CD4 and CD8 T cells. To address this issue, we have investigated B10.Q mice deficient for CD4 or CD8. The mice lacking CD4 were found to be less susceptible to disease, but not completely resistant, whereas the CD8 deficiency had no significant impact on the disease. No difference in the development of late occurring relapses was noted. Interestingly, the CD4-deficient mice had a severely reduced response to the glycosylated form of the immunodominant type II collagen (CII) 256–270 peptide whereas the response to the non-glycosylated peptide was not significantly different. Furthermore, CD4-deficient mice had lower antibody responses to CII, explaining the lower disease susceptibility. In comparison with previously reported results, it is apparent that the lack of CD4 molecules has a different impact on CIA if present on different genetic backgrounds, findings that could possibly be related to the occurrence of different disease pathways of CIA in different mouse strains.
|
|
| 7. |
- Holmdahl, Meirav, et al.
(author)
-
Primed B cells present type-II collagen to T cells.
- 2002
-
In: Scandinavian Journal of Immunology. - : Wiley. - 1365-3083 .- 0300-9475. ; 55:4, s. 382-389
-
Journal article (peer-reviewed)abstract
- Development of type-II collagen (CII)-induced arthritis (CIA) is dependent on a T-cell mediated activation of autoreactive B cells. However, it is still unclear if B cells can present CII to T cells. To investigate the role of B cells as antigen-presenting cells (APCs) for CII, we purified B cells from lymph nodes of immunized and nonimmunized mice. These B cells were used as APC for antigen-specific T-cell hybridomas. B cells from naïve mice did present native, triple-helical, CII (nCII) but also ovalbumin (OVA) and denatured CII (dCII) to antigen-specific T-cell hybridomas. In addition, B cells primed with nCII or OVA, but not dCII, activated the antigen-specific T-cell hybridomas two to three times better than naïve B cells. We conclude that antigen-primed B cells have the capacity to process and present CII to primed T cells, and antigen-primed antigen-specific B cells are more efficient as APC than naïve B cells. We further conclude that B cells have the potential to play an important role as APC in the development of CIA.
|
|
| 8. |
- Huang, Jason C., et al.
(author)
-
Analysis of autoreactive T cells associated with murine collagen-induced arthritis using peptide-MHC multimers.
- 2004
-
In: International Immunology. - : Oxford University Press (OUP). - 1460-2377. ; 16:2, s. 283-293
-
Journal article (peer-reviewed)abstract
- CD4+ T cells that recognize residues 256–270 of type II collagen (CII) associated with the I-Aq (Aq) molecule play a central role in disease pathogenesis in murine collagen-induced arthritis (CIA). Disease is most efficiently induced by immunization with heterologous CII, which elicits heterologous, e.g. bovine, CII256–270:I-Aq-specific T cells that only poorly cross-react with mouse CII. The self-epitope differs from heterologous CII256–270 by a conservative change of glutamic acid (heterologous) to aspartic acid (mouse) at position 266 which confers a lower affinity for binding to the I-Aq molecule. To date, characterization of the nature of T cell recognition in this model has been hindered by the lack of suitable, labeled multimeric peptide–MHC class II complexes. Here, we describe the biochemical properties of both recombinant bovine CII256–270:I-Aq (bCII256–270:I-Aq) and mouse CII256–270:I-Aq (mCII256–270:I-Aq) complexes, and use these as fluorescently labeled multimers (tetramers) to characterize the specificity of CII-reactive T cells. Our analyses show that an unexpectedly high percentage of bCII256–270:I-Aq-specific T cells are cross-reactive with mCII256–270:I-Aq. Interestingly, one T cell clone which has a relatively high avidity for binding to self-CII256–270:I-Aq shows a marked increase in binding avidity at physiological temperature, indicating that this TCR has unusual thermodynamic properties. Taken together, our analyses suggest that the low affinity of mCII256–270 for I-Aq may lead to a state of ignorance which can be overcome by priming CII-specific T cells with heterologous CII. This has relevance to understanding the mechanism by which CIA is induced and provides an explanation for the low arthritogenicity of mouse CII.
|
|
| 9. |
- Johansson, Åsa, et al.
(author)
-
Non-Major Histocompatibility Complex dependent variations in lymphocyte activity between inbred mouse strains susceptible to various autoimmune diseases
- 2000
-
In: Scandinavian Journal of Immunology. - : Wiley. - 0300-9475 .- 1365-3083. ; 52:1, s. 21-29
-
Journal article (peer-reviewed)abstract
- Transgenic techniques in inbred mouse strains are powerful tools to investigate the specific roles of genes in biological pathways and disease models. However, there is increasing concern over the influence of a variable genetic background in such experiments. To date there have been few investigations of the immunological differences between inbred mouse strains used in models of autoimmune diseases. Here we phenotyped lymph node cells and T-cell cytokine production in B10.Q (H2q), B10.RIII (H2r), C3H.Q (H2q), C3H. NB (H2p), NOD (H2g7), RIII/SJ (H2r) and DBA/1J (H2q) mice. We found several significant differences. The C3H strains and RIII/SJ lymph node cells had a high ratio of T cells/B cells (> 2 : 1) and a high ratio of CD4/CD8 positive cells (> 3 : 1), these strains are therefore denoted high T cell ratio (HiTR) strains. B10 strains and DBA/1, however, displayed an expansion of gammadeltaT cells after mitogen activation. T cells derived from C3H and DBA/1J strains produced more interleukin (IL)-4 than did T cells from B10 and NOD strains. DBA/1J and B10.Q showed a 10-fold increase in interferon (IFN)-gamma producing cells in the CD4+ T-cell population. Variation in the number of IL-2 and IFN-gamma producing T cells between the B10 major histocompatibility complex (MHC) congenic strains was the only difference possibly controlled by the MHC region. We conclude that non-MHC genes influence the numbers of T cells and B cells in lymph nodes, as well as IFN-gamma, IL-4 and IL-10 production by T cells.
|
|
| 10. |
- Kjellen, Peter, et al.
(author)
-
The H2-Ab gene influences the severity of experimental allergic encephalomyelitis induced by proteolipoprotein peptide 103-116
- 2001
-
In: Journal of Neuroimmunology. - 1872-8421. ; 120:1-2, s. 25-33
-
Journal article (peer-reviewed)abstract
- Immunization of H2(p) and H2(q) congenic C3H mouse strains with the PLP 103-116 peptide elicited two distinct experimental allergic encephalomyelitis (EAE) disease courses. C3H.Q (H2(q)) mice developed an acute-phase disease with classical ascending paralytic signs whereas C3H.NB (H2(p)) developed a highly variable disease course with symptoms originating from CNS above the spinal chord. C3H.Q lacks functional H2-E molecules and share H2-Aalpha with C3H.NB. To examine if the differences found at positions 85, 86, 88, and 89 in the Abeta-chains account for disease susceptibility, H2(q) mice were made transgenic with the Ab(p) gene. The Ab(p)-transgenic mice on the C3H.Q background developed a more severe disease course, demonstrating the importance of class II. However, the onset was not affected and the disease showed a classical ascending paralysis similar to the C3H.Q suggesting that the observed brain symptoms were related to nonclass II genes. Inhibition studies performed on affinity purified MHC class II molecules indicated that the PLP 103-116 peptide bound to A(p) with slightly higher affinity than to A(q). Both A(q) and A(p) formed long-lived stable complexes (t(1/2)>24 h) with the PLP 103-116 peptide, but a higher amount of the peptide was loaded on to A(p) compared with A(q). An F2 gene segregation experiment, in which the low PLP 103-116 binding A(r) molecule and the high binding A(p) molecule could be compared for the influence on the disease susceptibility, indicated a role for both peptide binding affinity and non-MHC genes. Based on our results, we conclude that the H2-Ab gene controls severity of EAE but not necessarily the onset or type of disease course and that affinity of the disease-promoting peptide for the class II molecule is a critical pathogenic factor.
|
|
| 11. |
- Lindgren, Mikael, et al.
(author)
-
Electronic states and phosphorescence of dendron functionalized platinum(II) acetylides
- 2007
-
In: Journal of Luminescence. - : Elsevier BV. - 0022-2313 .- 1872-7883. ; 124:2, s. 302-310
-
Journal article (peer-reviewed)abstract
- The photophysical properties of bis((4-(phenylethynyl)phenyl)ethynyl)bis(tributylphosphine) platinum(II) with 2,2-bis(methylo])propionic acid (bis-MPA) dendritic substituents were studied. The fluorescence emission decay upon excitation in the UV (typically 350-380 nm) was rapid, in the order of I ns or shorter. In oxygen-saturated tetrahydrofuran solvent, the phosphorescence decay time was in the order of 200 ns. Bright phosphorescence at 530 nm was found for dendrimers under certain conditions. The associated phosphorescence decay time considerably increased to above 100-200 mu s at higher concentrations (30-100 mu M), and in oxygen-evacuated samples. Thus, it was clarified that the strongest triplet quenching was caused by oxygen dissolved in the sample, since it was possible to reversibly go between the bright and quenched phosphorescent state by freeze-thaw pumping cycles. The bright phosphorescence formed spontaneously for the cases with the larger dendritic substituents is implying a chromophore protecting effect. From time-dependent density functional calculations, the electronic structure of a few low-lying singlet and triplet states are discussed. A new mechanism for efficient triplet state formation and phosphorescence of Pt-ethynyls is proposed. Here, a fast relaxation via internal conversion takes the excited population of the dominant pi -> pi*, excitation into a lower singlet state of ligand-to-metal charge transfer character of pi sigma* type. This allows an efficient inter system crossing to the triplet state manifold.
|
|
| 12. |
|
|
| 13. |
- Nandakumar, Kutty Selva, 1965-, et al.
(author)
-
Collagen type II (CII)-specific antibodies induce arthritis in the absence of T or B cells but the arthritis progression is enhanced by CII-reactive T cells
- 2004
-
In: Arthritis Research & Therapy. - : Springer Science and Business Media LLC. - 1478-6362 .- 1465-9905. ; 6:6
-
Journal article (peer-reviewed)abstract
- Antibodies against type II collagen (anti-CII) are arthritogenic and have a crucial role in the initiation of collagen-induced arthritis. Here, we have determined the dependence of T and B cells in collagen-antibody-induced arthritis (CAIA) during different phases of arthritis. Mice deficient for B and/or T cells were susceptible to the CAIA, showing that the antibodies induce arthritis even in the absence of an adaptive immune system. To determine whether CII-reactive T cells could have a role in enhancing arthritis development at the effector level of arthritis pathogenesis, we established a T cell line reactive with CII. This T cell line was oligoclonal and responded to different post-translational forms of the major CII epitope at position 260-270 bound to the Aq class II molecule. Importantly, it cross-reacted with the mouse peptide although it is bound with lower affinity to the Aq molecule than the corresponding rat peptide. The T cell line could not induce clinical arthritis per se in Aq-expressing mice even if these mice expressed the major heterologous CII epitope in cartilage, as in the transgenic MMC (mutated mouse collagen) mouse. However, a combined treatment with anti-CII monoclonal antibodies and CII-reactive T cells enhanced the progression of severe arthritis.
|
|
| 14. |
- Nyström, Andreas, et al.
(author)
-
Porphyrin-Cored 2,2-Bis(methylol)propionic Acid Dendrimers
- 2004
-
In: Chemistry of Materials. - : American Chemical Society (ACS). - 0897-4756 .- 1520-5002. ; 16:14, s. 2794-2804
-
Journal article (peer-reviewed)abstract
- The synthesis and characterization of dendron-coated porphyrins up to the fifth generation are described. Both free base and zinc-cored tetraphenylporphyrin (TPPH2 and TPPZn) were used, from which the dendrons were divergently grown using the anhydride of acetonide-protected bis-MPA (acetonide-2,2-bis(methoxy)propanoic anhydride). It is shown that a spacer must be attached to the porphyrin to increase the hydrolytic stability and allow synthesis of higher generations. Direct coupling of dendrons to the porphyrins was also investigated but failed to give full substitution of the porphyrin core. The absorption and fluorescence emission data for the TPPZn dendrimers indicate that the porphyrin configuration may change at higher generations. The hydrodynamic volume of the dendrimers is calculated from the polarization anisotropy decay data. It is shown that these bis-MPA dendrimers are significantly smaller than the same generation Frechet-type benzyl ether TPP dendrimer.
|
|
| 15. |
- Pizzolla, Angela, et al.
(author)
-
CD68-expressing cells can prime T cells and initiate autoimmune arthritis in the absence of reactive oxygen species.
- 2011
-
In: European Journal of Immunology. - : Wiley. - 1521-4141 .- 0014-2980. ; 41:2, s. 403-412
-
Journal article (peer-reviewed)abstract
- It is widely believed that DC, but not macrophages, prime naïve T cells in vivo. Here, we investigated the ability of CD68-expressing cells (commonly defined as macrophages) in priming autoreactive T cells and initiating collagen-induced arthritis (CIA) in the mouse. For this purpose, a transgenic mouse was developed (MBQ mouse) where macrophages exclusively expressed the MHC class II H2-A(q) (A(q) ) on an H2-A(p) (A(p) ) background. A(q) , but not A(p) expression mediates susceptibility to CIA through presentation of type II collagen (CII) to T cells. CIA severity is enhanced by a mutation in the Ncf1 gene, impairing reactive oxygen species (ROS) production by the phagocyte NADPH oxidase (NOX2) complex. Expression of functional Ncf1 on macrophages was previously shown to protect from severe CIA. To study the effect of ROS on macrophage-mediated priming of T cells, the Ncf1 mutation was introduced in the MBQ mouse. Upon CII immunization, Ncf1-mutated MBQ mice, but not Ncf1 wild-type MBQ mice nor Ncf1-mutated A(p) mice, activated autoreactive T cells and developed CIA. These findings demonstrate for the first time that macrophages can initiate arthritis and that the process is negatively regulated by ROS produced via the NOX2 complex.
|
|
| 16. |
- Råberg, Lars, et al.
(author)
-
Basal metabolic rate and the evolution of the adaptive immune system
- 2002
-
In: Royal Society of London. Proceedings B. Biological Sciences. - : The Royal Society. - 1471-2954. ; 269:1493, s. 817-821
-
Journal article (peer-reviewed)abstract
- Vertebrates have evolved an adaptive immune system in addition to the ancestral innate immune system. It is often assumed that a trade-off between costs and benefits of defence governs the evolution of immunological defence, but the costs and benefits specific to the adaptive immune system are poorly known. We used genetically engineered mice lacking lymphocytes (i.e. mice without adaptive, but with innate, immunity) as a model of the ancestral state in the evolution of the vertebrate immune system. To investigate if the magnitude of adaptive defence is constrained by the energetic costs of producing lymphocytes etc., we compared the basal metabolic rate of normal and lymphocyte-deficient mice. We found that lymphocyte-deficient mice had a higher basal metabolic rate than normal mice with both innate and adaptive immune defence. This suggests that the evolution of the adaptive immune system has not been constrained by energetic costs. Rather, it should have been favoured by the energy savings associated with a combination of innate and adaptive immune defence.
|
|
| 17. |
- Vestberg, Mikael
(author)
-
MHC and Transgenic Mice. A study into polymorphism and function of class I and class II molecules
- 2001
-
Doctoral thesis (other academic/artistic)abstract
- Transplantation antigens encoded in the major histocompatibility complex (MHC) bind peptides and present them to T cells. We showed that mouse T cells expressing transgenic human CD8 can recognise human MHC class I. Expression on mature T cells is sufficient for activation in a mixed lymphocyte culture but expression both on thymocytes and mature T cells is necessary for peptide specific MHC restricted responses. Transgenic human MHC class I and CD8 double transgenic mice can mount an immune response to flu virus. The T cell response mounted to any given stimuli is highly dependent on MHC haplotype. While the MHC of mouse and man are rather well characterised the polymorphism in rat MHC have not been thoroughly investigated. We sequenced cDNAs for the RT1-D loci. Contrary to the human homologue HLA-DR, a single allele is common in many labororatory rat strains. Mice with the MHC class II Aq may develop arthritis after immunisation with type II collagen (CII), but Ap mice do not. Both these class II molecules can present unmodified collagen peptides but only Aq can present glycosylated forms. We compared binding of the CII peptides to class II Aq and Ap. The amino acids most important for binding class II were isoleucine in position 260 and phenylalanine in position 263. The difference between the Aq and Ap is flanking the binding site of I260. A transgene coding for the b-chain in Aq expressed in Ap mice enable them to respond to glycosylated CII peptides. However, when bred to mice with other MHC haplotypes a different pattern evolved. Only some a-chains could support cell surface expression of the transgene and none of the mice with mixed class II made a T cell response to CII. A sequence analysis of the a-chains showed replacement close to position 260 or 263 indicating a loss of peptide binding capacity as the reason for the non-responsiveness. While CD4 deficient mice still had some MHC class II restricted helper T cells the responses to glycosylated collagen peptides were diminished. MHC class II transgenic and gene deficient mice were immunised with CII and followed for development of arthritis. CD4 deficient, but not CD8 deficient, mice had a reduced incidence of the disease. C3H.NB mice transgenic for Aq developed arthritis but B10.P with the same transgene did not. After excluding effects on T cell activation and protective effects from sex hormones a transgene mediated effect on B cell function with a higher impact on B10.P mice was identified to be the likely reason for the resistance to collagen induced arthritis.
|
|
| 18. |
- Vestberg, Robert, et al.
(author)
-
Dendron Decorated Platinum(II) Acetylides for Optical Power Limiting
- 2006
-
In: Macromolecules. - : American Chemical Society (ACS). - 0024-9297 .- 1520-5835. ; 39:6, s. 2238-2246
-
Journal article (peer-reviewed)abstract
- The effect of dendritic substituents on a nonlinear optical chromophore for optical power limiting (OPL) has been investigated. Synthesis and characterization of bis((4-(phenylethynyl)phenyl)ethynyl)bis-(tributylphosphine) platinum(II) with dendritic end groups are described. Polyester dendrimers up to the fourth generation were grown divergently using the anhydride of 2,2-bis(methylol)propionic acid (bis-MPA). The introduction of the dendritic moieties onto the NLO chromophore enables further processing of the materials using polymeric and related techniques. OPL measurements performed at 532, 580, and 630 nm show that the OPL properties improve with increasing size of the dendritic substituent. It is also shown that the addition of the dendrons increase the OPL as compared to the nondecorated bis((4-(phenylethynyl)phenyl) ethynyl)bis-(tributylphosphine)platinum(II). By use of femtosecond z-scan measurements carried out at different pulse-repetition frequencies, it is shown that the two-photon absorption cross section is ∼10 GM. Using pulse repetition frequencies (100 kHz-4.75 MHz) so that the time between the pulses is comparable with the triplet excited lifetime, the z-scans become dominated by excited-state absorption of excited triplet states.
|
|
| 19. |
- Westlund, Robert, et al.
(author)
-
Click Chemistry for Photonic Applications : Triazole-Functionalized Platinum(II) Acetylides for Optical Power Limiting
- 2008
-
In: Journal of Materials Chemistry. - : Royal Society of Chemistry (RSC). - 0959-9428 .- 1364-5501. ; 18:2, s. 166-175
-
Journal article (peer-reviewed)abstract
- Three different triazole-containing platinum(ii) acetylide compounds were synthesized by click chemistry and evaluated for their use in optical power limiting (OPL) applications. The triazole unit was incorporated at three different positions within, or at the end of, the conjugation path of the chromophore. The aim is to explore the possibilities of using click chemistry to prepare dendronized chromophores, and to evaluate how the triazole structure affects the photophysical properties and the optical power limiting abilities of these acetylide compounds. It is shown that the concept of click chemistry can be used to attach branched monomer units to ethynyl-phenyl arms by Huisgen 1,3-dipolar cycloaddition, forming triazole units within the chromophore. Photophysical characterization of these triazole-containing materials shows an absorption maximum within the UV-A region and emission through both fluorescence and phosphorescence. Bright phosphorescence was emitted from argon purged samples, and decay measurements thereof showed triplet lifetimes of up to 100 μs. The results from the photophysical characterization suggest that the triazole does break the conjugation path, and in order to gain maximum optical limiting the triazole needs to be placed at the end of the conjugation. All three investigated triazole-containing platinum(ii) acetylides show good optical power limiting at 532 nm (10 ns pulse, f/5 set-up, 2 mm cells). The most efficient compound, with the triazole positioned at the end of the conjugation, reaches a defined clamping level of 2.5 μJ for a sample with a concentration of 50 mM in THF and a linear transmission above 80% at 532 nm. These data can be compared to the OPL properties of Zn-based porphyrins or derivatized thiophenes, reaching clamping levels of 6-15 μJ.
|
|
| 20. |
- Westlund, Robert, et al.
(author)
-
Multi-functionalized platinum(II) acetylides for optical power limiting
- 2006
-
In: Optical Materials in Defence Systems Technology III. - : SPIE-INT SOC OPTICAL ENGINEERING. - 9780819464996 ; , s. U87-U94
-
Conference paper (peer-reviewed)abstract
- Preliminary results on the optical power limiting properties of platinum(II) acetylides containing triazole units are presented. It is shown that the triazole units give a positive contribution to the limiting abilities of the platinum(H) acetylide and that this modified chromophore could have potential use in sensor protection devices. Moreover, this paper discusses how the versatile building block 2,2-bis(methylol)propionic acid (bis-MPA) can be used advantageously to functionalize nonlinear optical (NLO) platinum(H) acetylides. The bis-MPA units can be used to prepare dendritic substituents offering site isolation to the chromophore leading to improved clamping. The bis-MPA functionalization also improves the solubility of the platinum(H) acetylides in many organic solvents. The preparation of solid-state optical power limiters, where the NLO chromophore is inserted in an optically transparent matrix, is addressed. Again, the bis-MPA unit can be employed to increase the number of accessible end-groups to which matrix-compatible species can be attached. It is concluded that the hydroxy-functional platinum(II) acetylides can be modified to fit almost any matrix, organic or inorganic. Finally, depending on functionalization, it is possible to prepare doped glasses where the chromophore is either embedded in the matrix, or covalently bonded to the matrix.
|
|
| 21. |
|
|
