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| 2. |
- Belfrage, Hans, et al.
(författare)
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Combined activation of murine lymphocytes with staphylococcal enterotoxin and interleukin-2 results in additive cytotoxic activity
- 1994
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Ingår i: Cancer Immunology and Immunotherapy. - 1432-0851. ; 38:4, s. 71-265
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Tidskriftsartikel (refereegranskat)abstract
- This report demonstrates that in vitro activation of murine spleen cells with interleukin-2 (IL-2) or the bacterial superantigen staphylococcal enterotoxin A (SEA) results in different patterns of activation and function of cytotoxic cells. Lymphokine-activated killer activity and antibody-dependent cellular cytotoxicity (ADCC) are mainly mediated by IL-2 activated natural killer (NK) cells. SEA is the most powerful T cell mitogen known so far and retargets cytotoxic T lymphocytes (CTL) to tumors expressing major histocompatibility complex (MHC) class II in staphylococcal-enterotoxin-dependent cellular cytotoxicity (SDCC). Culture of mouse spleen cells with SEA led to expansion and activation of T cells, which demonstrated strong SDCC activity and some NK-like cytotoxicity after 5 days in culture. Cell sorting revealed that both CD8+ and CD4+ T cells mediated SDCC but the former were more effective. Phenotypic analysis showed that SEA preferentially stimulated and expanded T cells expressing T cell receptor V beta 11, in particular CD8+ T cells. Combined activation with SEA and IL-2 resulted in simultaneous induction of T and NK cell cytotoxicity. Moreover, IL-2 had additive effects on SEA-induced SDCC. Combined treatment with SEA and IL-2 might therefore be an approach to induce maximal cytotoxicity against tumors and to recruit both T and NK cells in tumor therapy.
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| 3. |
- Belfrage, Hans, et al.
(författare)
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Enhanced and prolonged efficacy of superantigen-induced cytotoxic T lymphocyte activity by interleukin-2 in vivo
- 1995
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Ingår i: Cancer Immunology and Immunotherapy. - 1432-0851. ; 41:2, s. 87-94
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Tidskriftsartikel (refereegranskat)abstract
- The bacterial superantigen, staphylococcal enterotoxin A (SEA) activates T cells with high frequency and directs them to lyse MHC-class-II-expressing cells in superantigen-dependent cell-mediated cytotoxicity (SDCC). Treatment of mice with SEA induced strong CD8+ T-cell(CTL)-mediated SDCC, as well as abundant cytokine production from CD4+ and CD8+ T cells. However, both cytotoxicity and cytokine release were transient. In contrast, combined treatment with SEA and recombinant interleukin-2 (rIL-2) increased peak levels and maintained CTL activity. These effects were concomitant with an increased number of SEA-reactive V beta 11+ T cells. Both the CD4+ and CD8+ populations contained higher frequencies of cells expressing IL-2 receptor (IL-2R) alpha beta, which suggests that continuous IL-2R signaling preserves its high expression and subsequently prevents loss of growth factor signals necessary for expansion of T cells. Although IL-2R expression was increased among both CD4+ and CD8+ cells, only the cytotoxic function of CTL, but not cytokine production from either CD4 or CD8, was augmented. These findings demonstrate that treatment with rIL-2 potentiates superantigen-induced cytotoxicity and maintains high CTL activity. rIL-2 might therefore be useful in improving superantigen-based tumor therapy.
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| 4. |
- Belfrage, Hans, et al.
(författare)
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Functionally involved cell surface antigens on murine lymphokine activated killer cells
- 1987
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Ingår i: Immunology Letters. ; 14:4, s. 8-293
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Tidskriftsartikel (refereegranskat)abstract
- To investigate the possible involvement of some cell surface structures on lymphoid cells in the functional activity of lymphokine activated killer (LAK) cells, a number of monoclonal antibodies (Mab) against such structures was studied for their ability to inhibit LAK activity in a standard cytotoxicity assay against the natural killer-insensitive target cell EL-4. Almost complete inhibition of LAK activity resulted from incubation with antibodies to the LFA-1 antigen, while blocking of the Lyt 2 antigen reduced cytotoxic activity about 50%. Mab to T-200 gave a weak and inconsistent inhibitory activity, while antibodies to Thy 1, L3T4, IL-2 receptor and MHC class I antigens were without effect. Mab to LFA-1 and Lyt 2 inhibited LAK activity towards EL-4, YAC-1 and differentiated F-9 teratocarcinoma cells, but did not affect LAK-mediated killing of undifferentiated F-9 cells. Experiments with separate preincubation of effector and target cells revealed that both LFA-1 and Lyt 2 inhibited LAK activity at the effector cell level only.
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| 5. |
- Belfrage, Hans, et al.
(författare)
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Prevention of superantigen induced down-regulation of T cell mediated cytotoxic activity by IL-2 in vivo. 1996 Accepted for publication in Immunology
- 1997
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Ingår i: Immunology. - 0019-2805. ; 90:2, s. 8-183
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Tidskriftsartikel (refereegranskat)abstract
- Administration of staphylococcal enterotoxin A (SEA) to mice induces profound activation, cytokine production and cytotoxic activity of both CD4+ and CD8+ T cells, but subsequently activated cells are deleted or become anergic. This study demonstrates that administration of interleukin-2 (IL-2) can prevent sea-induced hyporesponsiveness in CD8+ cytotoxic T lymphocytes (CTL). Repeated injections with sea every fourth day resulted in severely reduced cytotoxic activity in the spleen, which correlated with a reduced number of sea-responsive T-cell receptor (TCR)-V beta 11+ CD8+ cells. Studies of purified TCR-V beta 11+ CD8+ cells showed that they possessed intact cytotoxic activity per cell compared with cells from mice given a single injection of SEA, indicating that deletion was the main mechanism for the reduced cytotoxic activity. Combined treatment with SEA and IL-2 increased the number of cytotoxic cells in the spleen after each SEA injection and prevented the down-regulation of cytotoxic activity. Increased cytotoxic activity could be related to increased number and proliferation of CD8+ IL-2R alpha + cells, suggesting that administration of IL-2 maintained IL-2 responsiveness among CD8+ cells. Studies of sorted TCR-V beta 11+ CD8+ cells demonstrated that combined treatment with SEA and IL-2 also increased cytotoxic activity per cell compared with treatment with SEA alone. Taken together, IL-2 administration in vivo augmented SEA-induced expansion of T cells as well as the cytotoxic activity per CTL, and prevented SEA-induced cell deletion.
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| 6. |
- Belfrage, Hans, et al.
(författare)
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Prevention of superantigen-induced tolerance in vivo by interleukin-2 treatment. 1996 Submitted
- 1997
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Ingår i: Cancer Immunology and Immunotherapy. - 1432-0851. ; 44:2, s. 77-82
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Tidskriftsartikel (refereegranskat)abstract
- Injection of the superantigen staphylococcal enterotoxin A (SEA) activates both CD4+ and CD8+ T cells expressing certain families of T cell receptor (TCR) variable-region beta (V beta) chain. T cells respond with profound cytokine production and induction of cytotoxicity. Repeated injections, however, cause deletion and anergy of both CD4+ and CD8+ T cells, resulting in reduced frequency of SEA-responsive cells TCR-V beta11+ as well as reduced cytokine levels in serum upon challenge with SEA. Exogenous interleukin-2 (IL-2) in vivo rescued SEA-responsive CD4+ and CD8+ cells from SEA-induced deletion and/or increase expansion of SEA-primed cells as well as preventing downregulation of endogenous IL-2 production in vivo. Combined treatment with SEA and IL-2 also superinduced production of important cytokines for the cytotoxic function of T cells, tumour necrosis factor alpha, interferon gamma and IL-6, on a cellular level. These studies show that continuous stimulation with IL-2 in vivo could be useful for superantigen-based immunotherapy by induction of excessive T cell activation and by prevention of the development of T cell deletion and anergy.
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| 8. |
- Kalland, L. E., et al.
(författare)
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C-type related order in the defective fluorites La2Ce2O7 and Nd2Ce2O7 studied by neutron scattering and ab initio MD simulations
- 2016
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Ingår i: Physical Chemistry Chemical Physics. - : Royal Society of Chemistry (RSC). - 1463-9084 .- 1463-9076. ; 18:34, s. 24070-24080
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Tidskriftsartikel (refereegranskat)abstract
- This work presents a structural investigation of La2-xNdxCe2O7 (x = 0.0, 0.5, 1.0, 1.5, 2.0) using X-ray powder diffraction and total scattering neutron powder diffraction, analysed using Rietveld and the reverse Monte Carlo method (RMC). Ab initio molecular dynamics (MD) modelling is also performed for further investigations of the local order. The main intensities in the neutron diffraction data for the La2-xNdxCe2O7 series correspond to the fluorite structure. However, additional C-type superlattice peaks are visible for x > 0 and increase in intensity with increasing x. The Nd-containing compositions (x > 0) are best fitted with Rietveld analysis by using a combination of oxygen deficient fluorite and oxygen excess C-type structures. No indications of cation order are found in the RMC or Rietveld analysis, and the absence of cation order is supported by the MD modelling. We argue that the superlattice peaks originate from oxygen vacancy ordering and associated shift in the cation position away from the ideal fluorite site similar to that in the C-type structure, which is seen from the Rietveld refinements and the observed ordering in the MD modelling. The vacancies favour alignments in the , and especially the direction. Moreover, we find that such ordering might also be found to a small extent in La2Ce2O7, explaining the discernible modulated background between the fluorite peaks. The observed overlap of the main Bragg peaks between the fluorite and C-type phase supports the co-existence of vacancy ordered and more disordered domains. This is further supported by the observed similarity of the radial distribution functions as modelled with MD. The increase in long range oxygen vacancy order with increasing Nd-content in La2-xNdxCe2O7 corresponds well with the lower oxide ion conductivity in Nd2Ce2O7 compared to La2Ce2O7 reported earlier.
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