A MINORITY SUBPOPULATION OF CD4(-CELLS DIRECTS THE DEVELOPMENT NAIVE CD4(+) T-CELLS INTO IL-4-SECRETING CELLS() T)

The culture of CD4(+) T cells with immobilized anti-CD3 and IL-2 gener ated a population of cells that produced both IL-4 and lFN-gamma on re stimulation. In contrast, CD4(+) T cells stimulated with immobilized a nti-V beta 6 under otherwise identical culture conditions generated ce lls that produced IFN-gamma but not IL-4 on restimulation. This differ ence was likely a result of quantitative differences in the concentrat ion of responding T cells in the two cultures rather than to qualitati ve differences between the two Abs. Anti-CD3 induced development of IL -4 secreting cells required IL-4 during the primary stimulation. This endogenous IL-4 in primary cultures was produced by cells with a Mel-1 4(low), memory/activated phenotype but not by cells expressing the Mel -14(high), naive phenotype. However, co-cultures of Mel-14(high) and M el-14(low) populations marked with different Ly-5 allotypes demonstrat ed that nearly all of the IL-4-secreting cells that developed from pri mary cultures were generated from the Mel-14(high) population. Moreove r, Mel-14(high) T cells could generate IL-4-secreting cells only in th e presence of Mel-14(low) T cells or rIL-4. In addition, co-culture of CD4(+), Mel-14(low) T cells from IL-4-deficient mice with CD4(+), Mel -14(high) T cells from wild-type mice did not lead to the development of IL-4-secreting cells. Thus, IL-4, made by a minority population of previously differentiated CD4(+) T cells, can induce the development o f IL-4-secreting cells from the naive T cells but naive CD4(+) T cells themselves do not develop into IL-4-secreting cells.