肿瘤坏死因子-α 联合干扰素-γ 或白细胞介素-1在鸟分枝杆菌复合群感染诱导免疫抑制性巨噬细胞中的作用。

The role of tumour necrosis factor-alpha in combination with interferon-gamma or interleukin-1 in the induction of immunosuppressive macrophages because of Mycobacterium avium complex infection.

作者信息

Tomioka H, Maw W W, Sato K, Saito H

机构信息

Department of Microbiology and Immunology, Shimane Medical University, Izumo, Japan.

出版信息

Immunology. 1996 May;88(1):61-7. doi: 10.1046/j.1365-2567.1996.d01-654.x.

DOI:10.1046/j.1365-2567.1996.d01-654.x

PMID:8707352

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1456459/

Abstract

The role of some cytokines including tumour necrosis factor-alpha (TNF-alpha), interleukin-1 alpha (IL-1 alpha), interferon-gamma (IFN-gamma), transforming growth factor-beta (TGF-beta) and interleukin-6 (IL-6) in the generation of immunosuppressive macrophages (M phi s) in host spleen cells of Mycobacterium avium complex (MAC)-infected mice was studied. M phi populations with potent suppressor activity against concanavalin A (Con A)-induced mitogenesis of splenocytes (SPCs) were elicited not only in euthymic but also in athymic nude mice during MAC infection. The suppressor M phi s are, therefore, inducible not only through a T-cell-dependent mechanism but also through T-cell-independent mechanism. However, MAC-induced M phi s of athymic mice displayed about four times lower suppressor activity than those of euthymic mice, indicating that mature T cells are important for M phi activation to the highly immunosuppressive state. Anti-TNF, anti-IFN-gamma, and anti-TGF-beta antibodies (Abs) but not anti-IL-6 Ab inhibited in vivo generation of MAC-induced immunosuppressive M phi s, and the neutralizing efficacy was in the order of anti-IFN-gamma Ab > anti-TNF Ab > anti-TGF-beta Ab. The effects of TNF-alpha, IL-1 alpha, IL-6, and IFN-gamma alone or combinations of them upon the acquisition of the suppressor activity by cultured splenic M phi s were studied. When normal splenic M phi s were treated with each cytokine for 3 days, TNF-alpha, IFN-gamma, and IL-1 alpha alone caused a slight elevation of their suppressive activity. Treatment of the normal M phi s with the combination of either TNF-alpha+IL-1 alpha or TNF-alpha+IFN-gamma yielded a marked increase in the suppressor activity, followed by IL-1 alpha+IFN-gamma. These findings indicate the important roles of TNF-alpha, IFN-gamma, and IL-1 alpha in the generation of MAC-induced suppressor M phi s.

摘要

研究了包括肿瘤坏死因子-α（TNF-α）、白细胞介素-1α（IL-1α）、干扰素-γ（IFN-γ）、转化生长因子-β（TGF-β）和白细胞介素-6（IL-6）在内的一些细胞因子在鸟分枝杆菌复合体（MAC）感染小鼠宿主脾细胞中免疫抑制性巨噬细胞（Mφs）产生过程中的作用。在MAC感染期间，不仅在有胸腺的小鼠中，而且在无胸腺裸鼠中都诱导出了对刀豆蛋白A（Con A）诱导的脾细胞（SPCs）有丝分裂具有强大抑制活性的Mφ群体。因此，抑制性Mφ不仅可通过T细胞依赖机制诱导，也可通过T细胞非依赖机制诱导。然而，无胸腺小鼠中MAC诱导的Mφ的抑制活性比有胸腺小鼠的低约四倍，这表明成熟T细胞对于Mφ激活至高度免疫抑制状态很重要。抗TNF、抗IFN-γ和抗TGF-β抗体（Abs）可抑制MAC诱导的免疫抑制性Mφ在体内的产生，但抗IL-6抗体则无此作用，且中和效力的顺序为抗IFN-γ抗体>抗TNF抗体>抗TGF-β抗体。研究了单独的TNF-α、IL-1α、IL-6和IFN-γ或它们的组合对培养的脾Mφ获得抑制活性的影响。当用每种细胞因子处理正常脾Mφ 3天时，单独的TNF-α、IFN-γ和IL-1α会使其抑制活性略有升高。用TNF-α+IL-1α或TNF-α+IFN-γ组合处理正常Mφ会使抑制活性显著增加，其次是IL-1α+IFN-γ。这些发现表明TNF-α、IFN-γ和IL-1α在MAC诱导的抑制性Mφ产生过程中起重要作用。