ALLOREACTIVE GAMMA-DELTA THYMOCYTES UTILIZE DISTINCT COSTIMULATORY SIGNALS FROM PERIPHERAL T-CELLS

Interactions between CD28/CTLA-4 on T cells and CD80 (B7.1) and CD86 ( B7.2) counter receptors provide crucial costimulatory signals for TCR- alpha beta(+) lymphocytes. To test the role of CD28 in thymic developm ent and activation of TCR-gamma delta(+) T cells, we introduced the al loreactive V gamma 2V alpha 11.3 TCR into CD28-deficient mice (CD28(-/ -)). We show that positive and negative selection of gamma delta Tg th ymocytes proceeded normally in the absence of CD28. Although mature Tg gamma delta(+) thymocytes required a second costimulatory signal for proliferation, gamma delta(+) thymocytes from CD28(-/-) and CD28(+/-) littermates responded equally well to the alloantigen Tla(b). Alloreac tivity of CD28(-/-) and CD28(+/-) Tg gamma delta(+) thymocytes could n ot be blocked with mAbs against CD80 and CD86 ligands. Thus gamma delt a thymocytes utilize a costimulatory system during development and all oresponses that is independent of CD28/CD80 and CD28/CD86 interactions . By contrast to V gamma 2V alpha 11.3(+) thymocytes, alloreactivity o f V gamma 2V alpha 11.3(+) lymph node T cells depended on CD28 costimu lation and was severely impaired in CD28(-/-) mice. These data provide functional evidence that maturation and selection of gamma delta cell s is independent of CD28. These results also indicate that distinct co stimulatory pathways are operational in mature thymocytes and peripher al T cells.