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. J. Leukoc. Biol. 67: 817–824; 2000.