Effects of IL-12 on helper T cell-dependent immune responses in vivo.
The differentiation of naive T cells to the Th1 or Th2 subset of effector cells is regulated by the cytokines to which T cells are exposed at the time of antigenic stimulation. Mice immunized with a hapten-protein conjugate and treated systemically with IL-12 show a marked inhibition of IL-4-secreting cells and suppressed production of anti-hapten IgG1 Ab, as well as a marked enhancement of IFN-gamma-producing T cells. Thus, IL-12 is a potent inhibitor of Th2 differentiation and an inducer of Th1 development in vivo. The IFN-gamma-inducing effect of IL-12 is partially blocked by pretreatment of mice with anti-asialo GM1 (anti-NK cell) Ab, but anti-asialo GM1 does not abrogate any of the other systemic actions of IL-12. Furthermore, none of the effects of IL-12 is prevented by treating mice with neutralizing anti-IFN-gamma Abs. These results suggest that the effects of IL-12 may be mediated both via NK cell stimulation and by directly altering the differentiation patterns of T cells. Finally, a neutralizing anti-IL-12 Ab significantly inhibits Th1 responses to Ag, indicating that IL-12 may play an obligatory role in Ag-induced Th1 differentiation in vivo.
McKnight
A J
AJ
Department of Pathology, Brigham & Women's Hospital, Boston, MA 02115.
Zimmer
G J
GJ
Fogelman
I
I
Wolf
S F
SF
Abbas
A K
AK
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D000941:Antigens; D002454:Cell Differentiation / Q000276:immunology; D005260:Female; D006241:Haptens; D006433:Hemocyanins / Q000276:immunology; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000145:classification; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12; D007378:Interleukins / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000276:immunology*
D000906:Antibodies; D000941:Antigens; D006241:Haptens; D007074:Immunoglobulin G; D007378:Interleukins; C054401:trinitrophenyl keyhole limpet hemocyanin; D018664:Interleukin-12; D007371:Interferon-gamma; D006433:Hemocyanins