Independent regulation of IFN-gamma and tumor necrosis factor by IL-1 in human T helper cells.
The lymphokines IL-2 and IL-4 promoted the growth of human PHA-triggered T cells, but only IL-2 induced the production of IFN-gamma and TNF. The addition of purified monocytes strongly enhanced the production of IFN-gamma in IL-2-stimulated T cell cultures but did not influence the production of TNF or the level of T cell proliferation. The addition of IL-1 to T cells activated by PHA and optimal concentrations of IL-2 resulted in a strong induction of IFN-gamma production but had no influence on TNF production or T cell proliferation. IL-6 did not influence IFN-gamma or TNF production or T cell proliferation induced by PHA-IL-2 and did not modulate IL-1-induced IFN-gamma production. The production of IFN-gamma by CD4+ 45R+ Th cells was strongly enhanced by IL-1, whereas CD8+ T cells were less responsive to IL-1 and CD4+ 45R+ T cells were unresponsive to IL-1. We demonstrate, at the clonal level, that the optimal production of IFN-gamma by human Th cells requires both IL-1 and IL-2, whereas the production of TNF and T cell proliferation are induced by IL-2 alone. We suggest that IL-1 acts as a second signal for IFN-gamma production and that it may have an important function in regulating the pattern of lymphokines produced by T cell subsets during activation.
Fischer
H
H
Wallenberg Laboratory, Department of Tumor Immunology, University of Lund, Sweden.
Hedlund
G
G
Kalland
T
T
Sjögren
H O
HO
Dohlsten
M
M
D000943:Antigens, Differentiation / Q000032:analysis; D015704:CD4 Antigens / Q000032:analysis; D006649:Histocompatibility Antigens / Q000032:analysis; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis*; D007375:Interleukin-1 / Q000502:physiology*; D007376:Interleukin-2 / Q000502:physiology; D015847:Interleukin-4 / Q000502:physiology; D017493:Leukocyte Common Antigens; D008213:Lymphocyte Activation; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D000943:Antigens, Differentiation; D015704:CD4 Antigens; D006649:Histocompatibility Antigens; D007375:Interleukin-1; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D007371:Interferon-gamma; D017493:Leukocyte Common Antigens