Ia- macrophages and cytokine networks contribute to tumor-induced suppression of CD4+ autoreactive T cells.
Tumor growth changes the functions and phenotypes of macrophages (M phi) and T cells. Suppression of CD4+ T cell autoresponses during tumor growth was contributed primarily by M phi. Tumor-induced alterations in the abilities of these cells to mediate autorecognition were assessed through syngeneic mixed lymphocyte reaction (SMLR) assays. Tumor-bearing host (TBH) M phi were significantly more suppressive (60-90%) than normal host (NH) M phi, and this suppression was caused partly by reduced Ia expression. TBH Ia- M phi were significantly more suppressive (50-80%) than their NH counterparts. The suppression mechanism was controlled partly by prostaglandin E2 (PGE2), because treating cultures with indomethacin and titrated NH and TBH Ia- M phi led to increased T-cell responsiveness, although responsiveness never reached levels of assays containing unseparated M phi. Blocking studies using anti-interferon-gamma (anti-IFN-gamma) monoclonal antibodies (mAb), anti-interleukin 4 (anti-IL-4) mAb, and indomethacin suggested that IFN-gamma, IL-4, and PGE2 contributed to tumor-induced M phi-mediated suppression. Our results suggested that a quantitative shift in M phi phenotype and a qualitative shift in M phi function in addition to differences in cytokine-directed accessory activities are partly responsible for tumor-induced suppression CD4+ T cell autoresponses.
Walker
T M
TM
Department of Biology, Virginia Polytechnic Institute and State University, Blacksburg 24061-0406.
Yurochko
A D
AD
Burger
C J
CJ
Elgert
K D
KD
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D015551:Autoimmunity; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D015232:Dinoprostone / Q000502:physiology*; D005354:Fibrosarcoma / Q000150:complications / Q000276:immunology* / Q000473:pathology; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D007153:Immunologic Deficiency Syndromes / Q000209:etiology* / Q000473:pathology; D007371:Interferon-gamma / Q000502:physiology*; D015847:Interleukin-4 / Q000502:physiology*; D007959:Lymphocyte Culture Test, Mixed; D008264:Macrophages / Q000276:immunology / Q000502:physiology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C / Q000276:immunology; D010641:Phenotype
D000949:Histocompatibility Antigens Class II; D015847:Interleukin-4; D007371:Interferon-gamma; D015232:Dinoprostone