International Immunology, Vol 10, 1057-1065, Copyright © 1998 by Oxford University Press
R Wijesuriya, S Maruo, JP Zou, M Ogawa, K Umehara, M Yamashita, S Ono, H Fujiwara and T Hamaoka
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.
ARTICLES
B cell-mediated down-regulation of IFN-gamma and IL-12 production induced during anti-tumor immune responses in the tumor-bearing state
Biomedical Research Center, Osaka University Medical School, Suita, Japan.
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