Costimulator dependence of lymphokine secretion by naive and activated CD4+ T lymphocytes from TCR transgenic mice.

The role of costimulation in Ag-induced responses of naive and differentiated IL-2 and IL-4-producing CD4+ T cells has been examined using cells from mice expressing a transgenic TCR specific for cytochrome c (81-104) + I-Ek. IL-2 secretion by naive and pre-activated T cells is dependent on costimulation, because it is not induced with chemically fixed APCs and is significantly inhibited by the B7 antagonist, CTLA4-Ig. In contrast, IL-4 secretion by in vitro differentiated Th2-like cells is relatively independent of costimulators. Thus, the requirement for costimulation is related more to lymphokine secretion profiles than to the previous activation status of CD4+ T lymphocytes.