Gamma delta T cell responses to activated T cells in multiple sclerosis patients induced by T cell vaccination

Abstract

To explore the hypothesis that gamma delta T cells may regulate activated alpha beta T cells, we studied gamma delta T cell responses to alpha beta 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 gamma delta 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 gamma delta T cells. Our data demonstrate that in the majority of vaccinated MS patients gamma delta T cells expand upon stimulation with the vaccine cells. The responding gamma delta T cells were predominantly V delta 1(+)/V gamma 1(+), and represented diverse clonal origins. The gamma delta 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, TNF alpha and IL10. These results indicate that gamma delta T cells can be stimulated by activated alpha beta T cells, and that these gamma delta T cell responses are upregulaled after T cell vaccination. These findings suggest that gamma delta T cells are involved in peripheral mechanisms to control activated autoreactive T cells. (C) 1998 Elsevier Science B.V. All rights reserved.