Recently activated T cells are costimulation-dependent in vitro

While the prominent role of B7-mediated signaling in the activation of naiv e and resting T cells has been exhaustively demonstrated, it is unclear whe ther costimulation is required in the amplification of an initiated immune response. In this study we have developed a multistep culture system to inv estigate the costimulation requirements of recently activated alloreactive CD4(+) T cells and the outcome of allorecognition of B7-deficient, MHC clas s-II-expressing epithelial cells. The results show that following in vitro "priming" with allogeneic costimulation rich antigen presenting cells, T ce lls can be reactivated 60 proliferate only if B7-mediated costimulation is provided. Furthermore, recognition of antigen on B7-negative epithelial cel ls induced allospecific nonresponsiveness in the responder T cells. Finally , the nonresponsive state was not accompanied by IL-4 secretion and appeare d to be reversible, since T cell reactivity could be restored by short-term culture in the presence of IL-2. These observations suggest that "primed" T cells remain B7-dependent in vitro and are susceptible to functional inac tivation following costimulation-deficient antigen presentation. (C) 1999 A cademic Press.