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- Frostegård, Johan, et al.
(författare)
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Antibodies against Phosphorylcholine among New Guineans Compared to Swedes: An Aspect of the Hygiene/Missing Old Friends Hypothesis.
- 2017
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Ingår i: Immunological investigations. - : Informa UK Limited. - 1532-4311 .- 0882-0139. ; 46:1, s. 59-69
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Tidskriftsartikel (refereegranskat)abstract
- We here study antibodies against phosphorylcholine (anti-PC) which we reported to be inversely associated with atherosclerosis, cardiovascular disease (CVD), and autoimmune conditions. In previous studies, we determined that this inverse association is more pronounced at low levels with high risk and at high levels, with decreased risk. We compare individuals from Kitava, New Guinea (with low risk of these conditions), with Swedish controls.We studied a group of 178 individuals from Kitava (age 20-86), and compared those above age 40 (n = 108) with a group of age- and sex-matched individuals from a population based cohort in Sweden (n = 108). Traditional risk factors for CVD and fatty acids were determined. IgM, IgG, and IgA anti-PC were tested by enzyme-linked immunosorbent assay (ELISA).All anti-PC measures were significantly lower among Swedish controls as compared to Kitavans (p < 0.001), independent of traditional risk factors. Having low levels of anti-PC, defined as below 25th percentile of values among Swedish controls, was associated with this cohort after adjustment for other risk factors (OR 5.7, 95% CI 2.2-14.7 for IgM; OR 31.7, 95% CI 3.9-252 for IgA; and OR 11.1, 95% CI 2.4-51 for IgG).PC is highly exposed on microorganisms and helminths (common on Kitava) exposing much PC which humans and hominids may have been exposed to for millions of years. We propose that low anti-PC levels in the developed world could be a new aspect of the hygiene hypothesis, generating a pro-inflammatory and pro-atherosclerotic state.
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- Lindhqvist, Violetta, et al.
(författare)
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Comparison of the mitogenic activities of streptococcal protein-G and staphylococcal protein-A on human mononuclear cells
- 1989
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Ingår i: Immunological Investigations. - : Informa UK Limited. - 0882-0139 .- 1532-4311. ; 18:7, s. 919-930
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Tidskriftsartikel (refereegranskat)abstract
- In the present work we report data from experiments comparing the proliferative stimuli demonstrated by Streptococcal Protein-G and Staphylococcal Protein A on human peripheral blood mononuclear cells. Protein-G and Protein-A are presented to the cells in solution as well as linked to plastic or Sepharose beads, or incorporated within the cell wall of whole bacteria. The cellular response is measured by incorporation of 3H-thymidine in 72 hr cultures. The soluble and the immobilized forms of Protein-A, but not those of Protein-G, displayed high mitogenicity. Possible explanations for the absence of Protein-G induced mitogenicity are discussed.
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- Minang, Jacob T., et al.
(författare)
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ELIspot displays a better detection over ELISA of T helper (Th) 2-type cytokine-production by ex vivo-stimulated antigen-specific T cells from human peripheral blood
- 2008
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Ingår i: Immunological Investigations. - : Informa UK Limited. - 0882-0139 .- 1532-4311. ; 37:4, s. 279-291
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Tidskriftsartikel (refereegranskat)abstract
- Detection of cytokines secreted by ex vivo antigen-stimulated peripheral blood mononuclear cells (PBMC) by ELISA is hampered by low frequencies of specific T cells and cellular receptor consumption. We investigated if ELISpot, measuring cytokine production at the single cell level, facilitated a better detection of the Th2 cytokines IL-4 and IL-5. PBMC from nickel-allergic (n = 31) and non-allergic subjects (n = 10) were stimulated with nickel or tetanus toxoid (TT) and cytokine production assessed by ELISpot and ELISA. By IL-4 ELISpot, 74% of the allergic and 0% control subjects responded to nickel and 56% of all subjects to TT. ELISA detected IL-4 after nickel stimulation only in 13% of the allergic subjects. Also detection of TT-induced IL-5 was improved by ELISpot with 54% subjects responding versus 24% in ELISA. In contrast, detection of nickel-induced IL-5 was more comparable between methods, most likely due to the 7-fold higher IL-5 production per cell in response to nickel versus IT. The low IL-5 response to TT was associated with a higher induction of the down-regulatory cytokine IL-10 by TT as compared to nickel (p < 0.001). Overall, ELISpot displayed a better detection of IL-4 as well as low intensity IL-5 responses thus emphasizing the importance of selecting suitable methods for the measurement of cytokine production ex vivo.
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- Nezlin, Roald, et al.
(författare)
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Presence of IgG-CD4 complexes in the circulation
- 2008
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Ingår i: Immunological Investigations. - : Informa UK Limited. - 0882-0139 .- 1532-4311. ; 37:2, s. 153-162
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Tidskriftsartikel (refereegranskat)abstract
- Many proteins of various origins are able to form complexes with Immunoglobulin G using reaction sites formed by residues of constant domains. Studies of IgG complexes of non-immune nature are important as biologically active proteins could escape from the circulation forming complexes with IgG as well as with other serum proteins whose concentration in serum is high. A quantitative characterization of circulating complexes in various diseases could give valuable information on the development of pathological processes. Immunoglobulins G are widely used for the treatment of a number of diseases and it is essential to understand what proteins are present in the preparations beside IgG. In the present study CD4 T-cell membrane glycoprotein was found in complexes with human IgG molecules isolated from donor sera as well as from sera of SLE patients via a sensitive quantitative dot-blot assay. According to immunoblotting experiments the CD4 part of the complexes had a molecular mass of about 50 kDa and is composed from all four extracellular domains. The CD4 content of the complexes varied among the studied human sera. There was no difference in IgG-CD4 complex concentration between the SLE patients and healthy controls. The data support the assumption that IgG molecules are able to act as scavengers and eliminate various proteins from the circulation including soluble CD4 protein.
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- Souza, Pedro P. C., et al.
(författare)
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The role of cytokines in inflammatory bone loss
- 2013
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Ingår i: Immunological Investigations. - : Informa UK Limited. - 0882-0139 .- 1532-4311. ; 42:7, s. 555-622
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Tidskriftsartikel (refereegranskat)abstract
- Chronic inflammatory processes close to bone often lead to loss of bone in diseases such as rheumatoid arthritis, periodontitis, loosened joint prosthesis and tooth implants. This is mainly due to local formation of bone resorbing osteoclasts which degrade bone without any subsequent coupling to new bone formation. Crucial for osteoclastogenesis is stimulation of mononuclear osteoclast progenitors by macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor-kappa B ligand (RANKL) which induces their differentiation along the osteoclastic lineage and the fusion to mature, multinucleated osteoclasts. M-CSF and RANKL are produced by osteoblasts/osteocytes and by synovial and periodontal fibroblasts and the expression is regulated by pro-and anti-inflammatory cytokines. These cytokines also regulate osteoclastic differentiation by direct effects on the progenitor cells. In the present overview, we introduce the basic concepts of osteoclast progenitor cell differentiation and summarize the current knowledge on cytokines stimulating and inhibiting osteoclastogenesis by direct and indirect mechanisms.
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- Wang, Feng, et al.
(författare)
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Anti-CD44 Monoclonal Antibody Inhibits Heart Transplant Rejection Mediated by Alloantigen-primed CD4(+) Memory T Cells in Nude Mice
- 2010
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Ingår i: Immunological Investigations. - : Informa UK Limited. - 0882-0139 .- 1532-4311. ; 39:8, s. 807-819
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Tidskriftsartikel (refereegranskat)abstract
- Donor-reactive CD4(+) memory T cells threaten the survival of transplanted organs. In this study, we used anti-CD44 monoclonal antibody (mAb) to inhibit adoptively transferred B6-reactive CD4(+) memory T cells (BALB/c origin) and to induce tolerance of B6 hearts in nude mice. The median survival time (MST) of the grafts was 6 days in the isotype group, and more than 100 days in the group treated with 8 doses of anti-CD44 at four-day intervals. Histological analysis revealed that the mean rejection level was Grade 3 in the isotype group, and Grade 0 or 1 in the multi-dose anti-CD44 treatment group. Compared with the isotype group, the multiply treated anti-CD44 group had significantly decreased IL-2 and IFN-gamma expressions, while IL-10 and TGF-beta were increased in the serum and the graft. Foxp3 in the graft was also increased. These data demonstrate that alloreactive CD4(+) memory T cells mediate the destruction of allografts, and the adhesion molecule CD44 plays an important role in this course. Anti-CD44 mAb may promote the reduction of CD4(+) memory T cells and the production of regulatory T cells (Tregs). Furthermore, Tregs are maintained at a certain level while suppressing cellular immunity and inducing the grafts long-term survival in transplant recipients.
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- Xie, Baiyi, et al.
(författare)
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Combined Costimulation Blockade Inhibits Accelerated Rejection Mediated by Alloantigen-primed Memory T Cells in Mice
- 2009
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Ingår i: Immunological Investigations. - : Informa UK Limited. - 0882-0139 .- 1532-4311. ; 38:7, s. 639-651
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Tidskriftsartikel (refereegranskat)abstract
- Donor-reactive memory T cells threaten the survival of transplanted organs via multiple pathways. This study was undertaken to induce tolerance of cardiac allografts in mice, in which alloreactive memory T cells were adoptively transferred, by combined costimulatory blockade of both effector and memory T cells. We found that the median survival time (MST) of the grafts was 5.17 days in the untreated group, 10.33 days in the CTLA4Ig- and antiCD40L- treated (2-combined) group, and more than 100 days in the CTLA4Ig-, anti-CD40L-, anti-LFA-1-, and anti-OX40L-treated (4-combined) group. Histological analysis revealed that the mean rejection level was Grade 4 in the untreated group, Grade 3 in the 2-combined treatment group, and Grade 0 in the 4-combined treatment group. CD44(high) T cells were detected only in the untreated group. The in vitro proliferation of lymphocytes of both untreated and 2-combined group was higher than that of the 4-combined treatment group (p < 0.01). Compared with the untreated group, the expression levels of IL-2, IFN-gamma, and Foxp3 were lower in the 2-combined treatment group; the expression levels of these genes were the lowest in the 4-combined treatment group. IL-10 expression was significantly higher in the 4-combined treatment group than in the other groups. These results demonstrate the inhibition efficacy of combined costimulation blockade in accelerated-rejection models and the possible mechanisms underlying the suppression of cellular immunity in mice receiving grafts as well as in inducing the activation of IL-10-producing Tr1 cells in grafts.
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