B cell-mediated down-regulation of IFN-gamma and IL-12 production induced during anti-tumor immune responses in the tumor-bearing state.
Unfractionated spleen cells taken from tumor-bearing mice contained tumor-primed T cells which produced lymphokines such as IFN-gamma and IL-2 through collaboration with antigen-presenting cells (APC) binding tumor antigens when cultured in vitro. Here, we investigated the regulatory mechanisms underlying IFN-gamma production by T-APC interactions. Elimination of B cells from a splenic population of tumor-bearing mice resulted in enhanced IFN-gamma production. Adding B cells back into cultures down-regulated IFN-gamma production to almost the same levels as those induced by unfractionated spleen cells. IL-2 production was not enhanced by B cell depletion, but rather was significantly suppressed. IFN-gamma-selective up-regulation was due to an enhancement of IL-12 production because IL-12 was detected in B cell-depleted cultures and enhanced IFN-gamma production was prevented by addition of anti-IL-12 mAb or anti-CD40 ligand (CD40L) mAb capable of inhibiting CD40L-induced IL-12 production. These results indicate that B cells interfere with IFN-gamma production induced through interactions between anti-tumor T cells and APC, and this suppressive effect is based on the capacity of CD40+ B cells to down-regulate the CD40L-induced IL-12 production by APC.
Biomedical Research Center, Osaka University Medical School, Suita, Japan.
R
R
Wijesuriya
S
S
Maruo
J P
JP
Zou
M
M
Ogawa
K
K
Umehara
M
M
Yamashita
S
S
Ono
H
H
Fujiwara
T
T
Hamaoka
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000938:Antigen-Presenting Cells / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D019013:CD40 Antigens / Q000276:immunology; D023201:CD40 Ligand; D002469:Cell Separation; D002478:Cells, Cultured; D005260:Female; D005434:Flow Cytometry; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000378:metabolism; D018664:Interleukin-12 / Q000096:biosynthesis* / Q000276:immunology / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D008211:Lymphocyte Cooperation; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000276:immunology*; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D019013:CD40 Antigens; D007376:Interleukin-2; D008562:Membrane Glycoproteins; D023201:CD40 Ligand; D018664:Interleukin-12; D007371:Interferon-gamma