Alloantigenic stimulation bypasses CD28-B7 costimulatory blockade by an interleukin-2-dependent mechanism

Allogeneic leukocytes have been used as biological adjuvants for T cell-specific responses to tumor and recall antigens, but the mechanisms underlying this effect have not been fully understood. The present study investigates whether alloantigen stimulation of human T cells would bypass an in vitro T cell costimulatory dysfunction induced by CTLA4Ig blockage of CD28-B7 interaction. Here, we demonstrate that costimulation with intact allogeneic leukocytes plus viral antigen circumvented the inhibition of this costimulatory pathway via interleukin-2 (IL-2) production, resulting in the generation of influenza-specific cytotoxic T lymphocytes (CTL). The alloantigen-induced help for influenza-specific CTL generation did not require cell-to-cell contact between responding and allogeneic stimulator cells. These results suggest that alloantigens can be used to bypass defects in the CD28-B7 costimulatory pathway and, therefore, may contribute to understanding the mechanisms of alloantigen-induced restoration of T cell-mediated immunity.