Naive human T cells can be a source of IL-4 during primary immune responses.
IL-4 plays a key role in driving the differentiation of CD4+ Th precursors into Th2 cells, both in mice and in humans. The source of IL-4 during primary immune responses is, however, still debated. When IL-4 consumption in in vitro T cell cultures was blocked with a MoAb to the IL-4 receptor alpha-chain (IL-4Ralpha), it became evident that freshly isolated naive (CD45RO-) CD4+ T cells from adults or cord blood produce IL-4 upon activation with anti-CD3 and CD80. IL-4 production by naive T cells is strictly IL-2-dependent. Endogenous IL-4 activity in naive CD4+ T cell cultures modulates the production of interferon-gamma (IFN-gamma) on the one hand and IL-5 and IL-13 on the other hand in opposite directions, and it is partly responsible for the low IFN-gamma production by cord blood T cells. Comparison of the ratio of IL-4/IFN-gamma in supernatants of T cell cultures reveals a skewing towards IL-4 production by cord blood T cells, while naive T cells from (non-atopic) adults predominantly produce IFN-gamma. We conclude that CD4+ naive T cells can produce IL-4 without the need for Th2 differentiation, and therefore that they can be the initial source of IL-4 required at the time of priming for T cell differentiation into Th2 cells.
Bullens
D M
DM
Laboratory of Experimental Immunology, Department of Pathophysiology, Faculty of Medicine, Catholic University of Leuven (KUL), Belgium.
Rafiq
K
K
Kasran
A
A
Van Gool
S W
SW
Ceuppens
J L
JL
D000328:Adult; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D005312:Fetal Blood / Q000166:cytology; D006801:Humans; D007156:Immunologic Memory / Q000187:drug effects; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000037:antagonists & inhibitors; D015847:Interleukin-4 / Q000096:biosynthesis*; D008297:Male; D015375:Receptors, Interleukin-2 / Q000037:antagonists & inhibitors; D019948:Receptors, Interleukin-4 / Q000037:antagonists & inhibitors / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D016207:Cytokines; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D019948:Receptors, Interleukin-4; D015847:Interleukin-4; D007371:Interferon-gamma