Gammadelta T cell responses to activated T cells in multiple sclerosis patients induced by T cell vaccination.
To explore the hypothesis that gammadelta T cells may regulate activated alphabeta T cells, we studied gammadelta T cell responses to alphabeta T cell clones in Multiple Sclerosis (MS) patients who received attenuated autologous autoreactive T cells. We recently conducted a pilot study of T cell vaccination with myelin basic protein reactive T cells in MS. Since T cell vaccination upregulates the anti-vaccine T cell responses, we evaluated gammadelta T cell reactivity towards the vaccine in the vaccinated patients. Lymphocytes were stimulated in vitro with irradiated vaccine cells and the responding lines were checked for the presence of gammadelta T cells. Our data demonstrate that in the majority of vaccinated MS patients gammadelta T cells expand upon stimulation with the vaccine cells. The responding gammadelta T cells were predominantly Vdelta1+/Vgamma1+, and represented diverse clonal origins. The gammadelta T cells could not inhibit in vitro proliferation of the vaccine T cells and displayed low cytotoxic reactivity towards the vaccine clones. However, they produced high levels of IL2, TNFalpha and IL10. These results indicate that gammadelta T cells can be stimulated by activated alphabeta T cells, and that these gammadelta T cell responses are upregulated after T cell vaccination. These findings suggest that gammadelta T cells are involved in peripheral mechanisms to control activated autoreactive T cells.
Multiple Sclerosis Research Unit, Dr. L. Willems-Instituut, Diepenbeek, Belgium. pstiniss@luc.ac.be
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Stinissen
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Zhang
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Vandevyver
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Hermans
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Raus
D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D007167:Immunotherapy; D008213:Lymphocyte Activation / Q000502:physiology*; D009000:Monocytes / Q000276:immunology; D009103:Multiple Sclerosis / Q000276:immunology* / Q000628:therapy*; D010835:Phytohemagglutinins / Q000494:pharmacology; D010865:Pilot Projects; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism*; D012016:Reference Values; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism
D016207:Cytokines; D010835:Phytohemagglutinins; D016692:Receptors, Antigen, T-Cell, gamma-delta