IL-4 synthesis by in vivo-primed memory CD4+ T cells: II. Presence of IL-4 is not required for IL-4 synthesis in primed CD4+ T cells.
Previous studies have shown that the presence of IL-4 is required for the development of IL-4 synthesis in naive CD4+ T cells. The purpose of our current studies was to investigate the role of IL-4 in the development of IL-4 synthesis in primed memory T cells. We therefore examined CD4+ T cells taken from lymph nodes of BALB/c mice immunized with keyhole limpet hemocyanin (KLH) and restimulated in vitro with KLH. Our results with such primed resting CD4+ T cells programmed to produce IL-4 indicated that the production of IL-4 did not require the presence of IL-4 (although the presence of IL-2 was absolutely necessary), and was only slightly limited by the presence of anti-IL-4 MAb. These results with resting memory T cells were not biased by the presence of activated T cells already producing substantial quantities of IL-4, since we demonstrated that high-density memory T cells could produce IL-4 in the absence of IL-4, and because T cells that actively produce IL-4 do not persist in vivo very long after antigen exposure. These results indicate that IL-4 synthesis in T cells committed to IL-4 production can indeed occur in the absence of IL-4 when culture conditions have been optimized and suggest that therapies with anti-IL-4 MAb or with soluble IL-4 receptors designed to control the development of IL-4 synthesis in memory T cells from individuals exhibiting excessive IL-4 synthesis will be unsuccessful. Therefore, other therapies, for example, utilizing IL-12, will be required to modulate the relatively fixed programs in memory T cells that direct the development of cytokine synthesis.
DeKruyff
R H
RH
Department of Pediatrics, Stanford University, California 94305, USA.
Fang
Y
Y
Secrist
H
H
Umetsu
D T
DT
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D000941:Antigens / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D002478:Cells, Cultured; D006433:Hemocyanins / Q000494:pharmacology; D007156:Immunologic Memory; D007376:Interleukin-2 / Q000502:physiology; D015847:Interleukin-4 / Q000096:biosynthesis* / Q000276:immunology / Q000502:physiology; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C
D000276:Adjuvants, Immunologic; D000911:Antibodies, Monoclonal; D000941:Antigens; D007376:Interleukin-2; D015847:Interleukin-4; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin