Hu R, Oyaizu N, Than S, Kalyanaraman V S, Wang X P, Pahwa S
Department of Pediatrics, North Shore University Hospital-Cornell University Medical College, Manhasset, New York 11030, USA.
Clin Immunol Immunopathol. 1996 Sep;80(3 Pt 1):283-9. doi: 10.1006/clin.1996.0125.
Transforming growth factor-beta (TGF-beta) is a multifunctional cytokine secreted by many mononuclear cells in peripheral blood (PBMC) and has diverse effects on cellular and humoral immunity. Increased TGF-beta mRNA expression has been reported in PBMC of HIV-infected patients, but the mechanism by which HIV induces TGF-beta secretion is unknown. In this study, we observed that HIV gp160 could induce significant TGF-beta secretion and TGF-beta mRNA expression in PBMC from HIV-seronegative healthy donors. The cellular source of TGF-beta was attributed to non-T cells, presumably monocytes. Specificity of secreted TGF-beta was confirmed by the addition of anti-TGF-beta mAb which abrogated the proliferative response of CCL-64 cells by gp160-treated culture supernatants. Soluble CD4 blocked the gp160-induced TGF-beta production, suggesting that CD4-gp160 interaction is required to induce TGF-beta production. Our results suggest that HIV-1 gp160 may contribute to the immune defects in HIV infection by inducing TGF-beta secretion.
转化生长因子-β（TGF-β）是一种由外周血中许多单核细胞分泌的多功能细胞因子，对细胞免疫和体液免疫具有多种作用。据报道，HIV感染患者外周血单个核细胞（PBMC）中TGF-β mRNA表达增加，但HIV诱导TGF-β分泌的机制尚不清楚。在本研究中，我们观察到HIV gp160可诱导HIV血清学阴性健康供者PBMC中显著的TGF-β分泌和TGF-β mRNA表达。TGF-β的细胞来源归因于非T细胞，可能是单核细胞。通过添加抗TGF-β单克隆抗体证实了分泌的TGF-β的特异性，该抗体消除了gp160处理的培养上清液对CCL-64细胞的增殖反应。可溶性CD4阻断了gp160诱导的TGF-β产生，表明CD4与gp160的相互作用是诱导TGF-β产生所必需的。我们的结果表明，HIV-1 gp160可能通过诱导TGF-β分泌导致HIV感染中的免疫缺陷。
