IL-10 acts on the antigen-presenting cell to inhibit cytokine production by Th1 cells.
Murine IL-10 (cytokine synthesis inhibitory factor) inhibits cytokine production by Th1 cell clones when they are activated under conditions requiring the presence of APC. By preincubating APC with IL-10, we demonstrate that IL-10 acts principally on APC to inhibit IFN-gamma production by Th1 clones. Moreover, IL-10 is not active when Th1 cells are stimulated with glutaraldehyde-fixed APC, which also indicates that its action involves regulation of APC function. Furthermore, IL-10 inhibits cytokine synthesis by Th1 cells stimulated with the super-antigen Staphylococcus enterotoxin B, which does not appear to require processing. Flow microfluorimetry purified splenic or peritoneal B cells and macrophages, and B cell and macrophage cell lines can present Ag to Th1 clones. However, IL-10 acts only on sorted macrophages and the macrophage cell line to suppress IFN-gamma production by Th1 clones. IL-10 does not show this effect when B cells are used as APC. In contrast, IL-10 does not impair the ability of APC to stimulate cytokine production by Th2 cells. IL-10 does not decrease IFN-gamma-induced I-Ad levels on a macrophage cell line. Inasmuch as IL-10 also inhibits IL-2-induced IFN-gamma production by Th1 cells in an Ag-free system requiring only the presence of accessory cells, these data suggest that IL-10 may inhibit macrophage accessory cell function which is independent of TCR-class II MHC interactions.
Fiorentino
D F
DF
Department of Immunology, DNAX Research Institute, Palo Alto, CA 94304.
Zlotnik
A
A
Vieira
P
P
Mosmann
T R
TR
Howard
M
M
Moore
K W
KW
O'Garra
A
A
D000818:Animals; D000938:Antigen-Presenting Cells / Q000187:drug effects* / Q000276:immunology; D001402:B-Lymphocytes / Q000187:drug effects; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis*; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D007371:Interferon-gamma / Q000494:pharmacology; D016753:Interleukin-10; D007378:Interleukins / Q000494:pharmacology*; D008213:Lymphocyte Activation; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D006377:T-Lymphocytes, Helper-Inducer / Q000378:metabolism*
D016207:Cytokines; D000949:Histocompatibility Antigens Class II; D007378:Interleukins; D011948:Receptors, Antigen, T-Cell; D016753:Interleukin-10; D007371:Interferon-gamma