A minority subpopulation of CD4+ T cells directs the development of naive CD4+ T cells into IL-4-secreting cells.
The culture of CD4+ T cells with immobilized anti-CD3 and IL-2 generated a population of cells that produced both IL-4 and IFN-gamma on restimulation. In contrast, CD4+ T cells stimulated with immobilized anti-V beta 6 under otherwise identical culture conditions generated cells that produced IFN-gamma but not IL-4 on restimulation. This difference was likely a result of quantitative differences in the concentration of responding T cells in the two cultures rather than to qualitative 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-14low, memory/activated phenotype but not by cells expressing the Mel-14high, naive phenotype. However, co-cultures of Mel-14high and Mel-14low populations marked with different Ly-5 allotypes demonstrated that nearly all of the IL-4-secreting cells that developed from primary cultures were generated from the Mel-14high population. Moreover, Mel-14high T cells could generate IL-4-secreting cells only in the presence of Mel-14low T cells or rIL-4. In addition, co-culture of CD4+, Mel-14low T cells from IL-4-deficient mice with CD4+, Mel-14high 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 of IL-4-secreting cells from the naive T cells but naive CD4+ T cells themselves do not develop into IL-4-secreting cells.
Gollob
K J
KJ
DNAX Research Institute of Molecular and Cellular Biology Inc., Palo Alto, CA 94304.
Coffman
R L
RL
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D017252:CD3 Complex / Q000502:physiology; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000032:analysis; D002478:Cells, Cultured; D005260:Female; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000235:genetics / Q000378:metabolism*; D019041:L-Selectin; D051379:Mice; D008810:Mice, Inbred C57BL; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000502:physiology; D016176:T-Lymphocyte Subsets / Q000502:physiology*
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D015815:Cell Adhesion Molecules; D016693:Receptors, Antigen, T-Cell, alpha-beta; D019041:L-Selectin; D015847:Interleukin-4; D007371:Interferon-gamma