Interleukin-12 increases interleukin-4 production by established human Th0 and Th2-like T cell clones.
Interleukin (IL)-12 is a potent inducer of cell-mediated immunity: it favors the generation of interferon (IFN)-gamma-producing T cells, increases IFN-gamma production by T cells and natural killer cells and prevents the generation of a Th2 response in murine in vivo models. Nevertheless, the effects of IL-12 on an established Th2 response remain poorly documented. In the present paper, we analyzed the effect of IL-12 on the profile of lymphokines produced by established IL-4-producing Th0 and Th2-like human T cell clones (TCC) and by polyclonal T cells. We found that IL-12 (i) enhances, as previously reported, IFN-gamma production by Th0 TCC and, to a smaller extent, by Th2-like TCC, (ii) increases the proliferation of Th0 and Th2-like TCC and (iii) unexpectedly, synergizes with T cell receptor-associated or nonspecific stimuli in increasing IL-4 production by these TCC. Thus, IL-12 potentiates the production of IFN-gamma and also of IL-4 by established IL-4 producing TCC. Although IL-12 has been widely reported to induce a Th1 response and to prevent the development of a Th2 response in vivo, IL-12 may on the contrary potentiate an established Th2 response in humans.
Jeannin
P
P
Glaxo Institute for Molecular Biology, Plan les Ouates/Geneva, Switzerland.
Delneste
Y
Y
Life
P
P
Gauchat
J F
JF
Kaiserlian
D
D
Bonnefoy
J Y
JY
D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry; D002999:Clone Cells; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000502:physiology*; D015847:Interleukin-4 / Q000096:biosynthesis*; D008213:Lymphocyte Activation / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000378:metabolism*; D018418:Th2 Cells / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma