Tumor growth changes the contribution of granulocyte-macrophage colony-stimulating factor during macrophage-mediated suppression of allorecognition.
Tumor-bearing host (TBH) macrophages (M phi) suppress T cell alloresponses, and this study suggests granulocyte-macrophage colony-stimulating factor (GM-CSF), a molecule associated with suppressive M phi activity during tumor growth, signals more immunosuppression. In the absence of M phi, GM-CSF increased T cell proliferation in response to alloantigen. However, TBH M phi-mediated suppression of allorecogntion was further induced by GM-CSF. Allogeneic mixed lymphocyte reaction (MLR) cultures, containing normal host (NH) M phi, were either unaffected or enhanced. Prostaglandin E2 (PGE2), a highly suppressive monokine that decreases alloreactivity, did not seem to be involved in the suppression caused by the TBH M phi/GM-CSF interaction. M phi-CSF (M-CSF) addition to cultures did not reverse the suppression caused by TBH M phi and GM-CSF, and inhibition of PGE2 synthesis did not change the response to M-CSF. TBH Ia- M phi, a suppressor population that predominates among splenic M phi during tumor growth, demonstrated significantly lower reactivity in the presence of GM-CSF. In contrast, alloresponses suppressed by NH Ia- M phi demonstrated higher reactivity in the presence of GM-CSF. The data collectively suggest that TBH M phi respond differently to GM-CSF, and that tumor-induced changes in GM-CSF responsiveness affect M phi accessory ability.
Walker
T M
TM
Department of Biology, Virginia Polytechnic Institute and State University, Blacksburg.
Yurochko
A D
AD
Burger
C J
CJ
Elgert
K D
KD
D000818:Animals; D002478:Cells, Cultured; D015232:Dinoprostone / Q000502:physiology; D005354:Fibrosarcoma / Q000276:immunology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007108:Immune Tolerance; D007213:Indomethacin / Q000494:pharmacology; D007959:Lymphocyte Culture Test, Mixed; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D008264:Macrophages / Q000502:physiology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D013601:T-Lymphocytes / Q000276:immunology*
D000949:Histocompatibility Antigens Class II; D016173:Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D015232:Dinoprostone; D007213:Indomethacin