Recently activated T cells are costimulation-dependent in vitro.
While the prominent role of B7-mediated signaling in the activation of naive and resting T cells has been exhaustively demonstrated, it is unclear whether costimulation is required in the amplification of an initiated immune response. In this study we have developed a multistep culture system to investigate the costimulation requirements of recently activated alloreactive CD4(+) T cells and the outcome of allorecognition of B7-deficient, MHC class-II-expressing epithelial cells. The results show that following in vitro "priming" with allogeneic costimulation rich antigen presenting cells, T cells can be reactivated to proliferate only if B7-mediated costimulation is provided. Furthermore, recognition of antigen on B7-negative epithelial cells induced allospecific nonresponsiveness in the responder T cells. Finally, the nonresponsive state was not accompanied by IL-4 secretion and appeared 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 inactivation following costimulation-deficient antigen presentation.
Marelli-Berg
F M
FM
Department of Immunology, Imperial College School of Medicine at the Hammersmith Hospital, London, W12 0NN, United Kingdom.
Barroso-Herrera
O
O
Lechler
R I
RI
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002455:Cell Division; D002461:Cell Line, Transformed; D004847:Epithelial Cells / Q000276:immunology; D015793:HLA-B7 Antigen / Q000276:immunology*; D006801:Humans; D007376:Interleukin-2 / Q000276:immunology / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000276:immunology*
D015793:HLA-B7 Antigen; D007376:Interleukin-2