We have documented the inability of human corneal epithelial−like cells to suppress proliferation of peripheral blood leukocytes (PBLs) induced by allogeneic PBLs in a mixed leukocyte reaction (MLR). Instead, enhanced proliferation of PBLs, albeit small, was consistently noted as indicated by uptake of radiolabeled thymidine. Maximum proliferation of PBLs was detected when a mixed leukocyte reaction (MLR) was conducted in the presence of corneal cells. High levels of interleukin-1β(IL-1β) were found during MLR irrespective of the presence of corneal cells. High levels of IL-1β correlated well with observed synergistic stimulation of PBL proliferation by corneal cells and stimulating allogeneic PBLs. In PBL-corneal cell cocultures, PBLs produced IL-1β corneal cells contributed large amounts of prostaglandin E2 (PGE2). Although indomethacin completely blocked prostaglandin E2production, it did not significantly alter the results. Our data show that PBLs and corneal cells can reciprocate each other's presence, and, under appropriate conditions, corneal cells can deliver at least one signal to enhance rather than suppress antigen-driven PBL proliferation. Our data suggest a role for immunoregulatory cytokines and prostanoids such as IL-1β and PGE2 in these interactions.