Alloreactive γδ thymocytes utilize distinct costimulatory signals from peripheral T cells

Abstract

Interactions between CD28/CTLA-4 on T cells and CD80 (B7.1) and CD86 (B7.2) counter receptors provide crucial costimulatory signals for TCR- αβ+ lymphocytes. To test the role of CD28 in thymic development and activation of TCR-γδ+ T cells, we introduced the alloreactive Vγ2Vα11.3 TCR into CD28-deficient mice (CD28(-/-)). We show that positive and negative selection of γδ Tg thymocytes proceeded normally in the absence of CD28. Although mature Tg γδ+ thymocytes required a second costimulatory signal for proliferation, γδ+ thymocytes from CD28(-/-) and CD28(+/-) littermates responded equally well to the alloantigen Tlab. Alloreactivity of CD28(-/-) and CD28(+/-) Tg γδ+ thymocytes could not be blocked with mAbs against CD80 and CD86 ligands. Thus γδ+ thymocytes utilize a costimulatory system during development and alloresponses that is independent of CD28/CD80 and CD28/CD86 interactions. By contrast to Vγ2Vα11.3+ thymocytes, alloreactivity of Vγ2Vα11.3+ lymph node T cells depended on CD28 costimulation and was severely impaired in CD28(-/-) mice. These data provide functional evidence that maturation and selection of γδ cells is independent of CD28. These results also indicate that distinct costimulatory pathways are operational in mature thymocytes and peripheral T cells.