Antigen‐specific stimulation and trans‐stimulation of T cells in long‐term culture

Abstract

Abstract When T cells from antigen‐primed lymph nodes are stimulated in vitro with antigen, they give rise to a proliferative response as high as that elicited by the polyclonal T cell activator concanavalin A. It is likely that in these conditions not only antigen‐specific T cells proliferate. We have established an experimental system which demonstrates that large numbers of nonantigen‐specific T cells are induced to proliferate as a result of antigen‐specific T cells' confrontation with antigen. This phenomenon, which we call trans ‐ stimulation is antigen‐dependent and antigen‐specific. Although the presence of antigen‐specific T cells is required, these cells do not have to proliferate in order to induce trans‐stimulation. In an attempt to enrich for antigen‐specific T cells in vitro , we established conditions for culturing T cells in the presence of antigen for long periods of time (up to 6 weeks). High levels of antigen reactivity were observed upon antigen restimulation of “directly” stimulated T cells from long‐term cultures. In contrast, long‐term cultures of trans‐stimulated cells were depleted of antigen reactivity. Neither type of long‐term culture contained detectable alloreactive cells indicating that trans‐stimulation is not reflected randomly upon bystander T cells.