Walker T M, Yurochko A D, Burger C J, Elgert K D
Department of Biology, Virginia Polytechnic Institute and State University, Blacksburg.
Immunobiology. 1992 Sep;185(5):427-39. doi: 10.1016/S0171-2985(11)80085-9.
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.
荷瘤宿主（TBH）巨噬细胞（M phi）可抑制T细胞同种异体反应，本研究表明，粒细胞-巨噬细胞集落刺激因子（GM-CSF），一种在肿瘤生长过程中与抑制性M phi活性相关的分子，会引发更多免疫抑制。在没有M phi的情况下，GM-CSF可增加T细胞对同种异体抗原的增殖反应。然而，GM-CSF进一步诱导了TBH M phi介导的同种异体识别抑制。含有正常宿主（NH）M phi的同种异体混合淋巴细胞反应（MLR）培养物不受影响或增强。前列腺素E2（PGE2），一种高度抑制性的单核因子，可降低同种异体反应性，似乎不参与TBH M phi/GM-CSF相互作用引起的抑制。向培养物中添加M phi-CSF（M-CSF）并不能逆转TBH M phi和GM-CSF引起的抑制，抑制PGE2合成也不会改变对M-CSF的反应。TBH Ia- M phi是肿瘤生长期间在脾脏M phi中占主导地位的抑制性群体，在GM-CSF存在下其反应性显著降低。相比之下，由NH Ia- M phi抑制的同种异体反应在GM-CSF存在下表现出更高的反应性。这些数据共同表明，TBH M phi对GM-CSF的反应不同，并且肿瘤诱导的GM-CSF反应性变化会影响M phi的辅助能力。
