Distinct antigen presenting cell-derived signals induce TH cell proliferation and expression of effector cytokines

In addition to the stimulus delivered by the specific interaction of the T cell receptor (TCR) and the antigen - MHC class II complex, activation of resting helper T lymphocytes (TH) requires several poorly defined accessory cell-derived co-stimulatory signals. Here we provide evidence that proliferation and expression of effector cytokine genes by TH cells are induced by distinct co-stimulatory signals. Normal murine splenic TH cells were activated by Staphylococcus aureus enterotoxin B (SEB) superantigen and various antigen presenting cells (APCs) to proliferate, differentiate into TH cells blasts, and secrete cytokines. Blast transformation and proliferation of TH cells is achieved with macrophages and other splenic APCs, like B cells. Expression of the cytokines interferon gamma (IFN gamma), IL-5, and IL-2 by TH cells, however, is to various degrees dependent on the presentation of SEB by macrophages. The requirement for macrophages is particularly striking for the expression of IFN gamma. Thus macrophages provide distinct co-stimulatory signals for cytokine secretion and proliferation. The results suggest that B cells induce clonal expansion of TH cells whereas macrophages additionally promote terminal differentiation of activated TH cells into TH effector cells.