IA- MACROPHAGES AND CYTOKINE NETWORKS CONTRIBUTE TO TUMOR-INDUCED SUPPRESSION OF CD4-CELLS( AUTOREACTIVE T)

Tumor growth changes the functions and phenotypes of macrophages (Mphi ) and T cells. Suppression of CD4+ T cell autoresponses during tumor g rowth was contributed primarily by Mphi. Tumor-induced alterations in the abilities of these cells to mediate autorecognition were assessed through syngeneic mixed lymphocyte reaction (SMLR) assays. Tumor-beari ng host (TBH) Mphi were significantly more suppressive (60-90%) than n ormal host (NH) Mphi, and this suppression was caused partly by reduce d la expression. TBH la- Mphi were significantly more suppressive (50- 80%) than their NH counterparts. The suppression mechanism was control led partly by prostaglandin E2 (PGE2), because treating cultures with indomethacin and titrated NH and TBH la- Mphi led to increased T-cell responsiveness, although responsiveness never reached levels of assays containing unseparated Mphi. Blocking studies using anti-interferon-g amma (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 Mphi-mediated suppression. Our resul ts suggested that a quantitative shift in Mphi phenotype and a qualita tive shift in Mphi function in addition to differences in cytokine-dir ected accessory activities are partly responsible for tumor-induced su ppression CD4+ T cell autoresponses.