IL-12 activates IFN-gamma production through the preferential activation of CD30+ T cells.
CD30 is normally expressed by a subset (15 to 20%) of CD45RO+ T cells after activation by a variety of T cell stimuli and defines the principal IFN-gamma-producing T cells subset. Inasmuch as the production of IFN-gamma is regulated by IL-2 and IL-12, we have examined the effects of these cytokines on the proliferation, induction, and function of CD30+ and CD30- T cell subsets. Upon isolation, CD30+CD25+ T cells exhibit high levels of baseline proliferation compared with CD30-CD25+ T cells. Neutralizing Abs specific for IL-2, IL-4, IL-6, or IL-12 had no effect on basal levels of proliferation in CD30+CD25+ T cells, whereas anti-IL-2 inhibited the basal proliferative activity of CD30-CD25+ T cells. The addition of exogenous rIL-12 to purified CD30+CD25+ and CD30-CD25+ T cells subsets induced significantly higher maximal levels of proliferation in the CD30+ subset, whereas rIL-2 supported comparable levels of maximal proliferation in each subset. The addition of rIL-2 to anti-CD3-activated PBMC increased the relative numbers of CD30+ T cells by expansion of CD30+ T cells, as opposed to recruitment of CD30+ T cells from the CD30- population. Furthermore, the development of the CD30+ T cell subset was inhibited by either anti-IL-2, anti-IL-12, or rIL-10. Inhibition by anti-IL-2 and rIL-10 was overcome by the addition of rIL-12, but not IL-2, to the cultures. Finally, rIL-12 increased IFN-gamma production by CD30+ T cells, yet had little effect on IFN-gamma production by CD30- T cells. Thus, CD30+ T cells are preferentially regulated by IL-12, and the effects of IL-12 on T cell IFN-gamma production are mediated largely through its effects on the CD30+ subset.
Alzona
M
M
Division of Hematology/Oncology, Loyola University School of Medicine, Maywood, IL 60153.
Jäck
H M
HM
Fisher
R I
RI
Ellis
T M
TM
D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis*; D018664:Interleukin-12 / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology; D017730:Ki-1 Antigen / Q000032:analysis; D008213:Lymphocyte Activation / Q000187:drug effects; D011994:Recombinant Proteins / Q000494:pharmacology; D013268:Stimulation, Chemical; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism
D007376:Interleukin-2; D017730:Ki-1 Antigen; D011994:Recombinant Proteins; D018664:Interleukin-12; D007371:Interferon-gamma