Cellular and humoral immune responses against autoreactive T cells in multiple sclerosis patients after T cell vaccination

Myelin basic protein (MBP)-reactive T cells may play an important role in t he autoimmune pathogenesis of multiple sclerosis (MS). MBP-reactive T cells can be specifically targeted by T cell vaccination, a procedure whereby MS patients are immunized with attenuated autologous MBP reactive T cells. T cell vaccination induces immune responses to the vaccine cells together wit h a depletion of MBP reactive T cells. Forty-nine MS patients were treated with T cell vaccination in an extended phase I trial to study the safety, i mmune responses and clinical effects of T cell vaccination. In the present paper the immune responses towards the vaccine cells were characterized. Su bstantial long-term in vitro proliferative responses were observed in all t reated patients. Some patients, immunized with different clones, displayed distinct proliferative reactivity against the various vaccine clones, sugge sting unequal immunogenic properties of these clones. Reactive TCR alpha be ta(+), CD8(+) and CD4(+) T cells, and to a lesser extent, gamma delta T cel ls and NK cells were observed to in vitro stimulation with the vaccine cell s. A small fraction only of CD8(+) T cells expressed cytolytic and inhibito ry anti-clonotypic reactivity against the vaccine cells. Stimulation with t he vaccine clones predominantly induced expression of pro-inflammatory cyto kines in these mixed cultures, although one vaccine clone consistently indu ced production of IL-4. CD4(+) T cells are the major cytokine-producing cel ls in these anti-vaccine lines. We could not detect upregulated antibody re sponses to the vaccine cells in most patients, although a temporary antibod y response was observed in one patient. In conclusion, immunization with at tenuated autoreactive T cells induces a complex cellular response specifica lly targeted at the vaccine cells, but no antibody responses. These data pr ovide further insights into the mechanisms of T cell vaccination and improv e our understanding of the complex regulatory networks of autoreactive T ce lls. (C) 1999 Academic Press.