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.