Uittenbogaart C H, Boscardin W J, Anisman-Posner D J, Koka P S, Bristol G, Zack J A
Department of Pediatrics, the UCLA AIDS Institute, UCLA School of Medicine, Los Angeles, California 90095-1747, USA.
AIDS. 2000 Jul 7;14(10):1317-25. doi: 10.1097/00002030-200007070-00003.
Cytokines play an important role in the differentiation of thymocytes into mature T cells; consequently, certain cytokines could be useful for immune reconstitution after HIV infection without increasing viral load.
To investigate whether cytokines affect immune depletion caused by HIV infection with a CXCR4-tropic strain in SCID-hu mice implanted with human fetal thymus and liver (thy/liv) tissue.
The thy/liv implants were either mock infected or infected with HIV-1 NL4-3, a CXCR4-tropic molecular clone. Interleukin (IL)-2, IL-4, IL-7, interferon-gamma (IFN-gamma) or diluent was administered to the mice during the second and third week postinfection. Viral load and immunophenotype were determined in thymocytes.
Thymocyte subset distributions at 3 weeks postinfection were significantly influenced by treatment with certain cytokines. In particular, IL-2 caused the infected mice to retain a thymocyte profile that was more similar to that in mock-infected mice than that in diluent-treated infected mice, in that the percentages of immature CD4+CD8+ and CD5+CD1+ cells were slightly higher and much less variable than in diluent-treated infected mice. The effect of IFN-gamma treatment was similar to IL-2 but did not reach statistical significance. However, after IFN-gamma treatment, normal percentages of mature CD3+CD69+ cells were maintained whereas this population was relatively increased in diluent-treated infected mice. Although treatment with IL-4 and IL-7 delayed depletion of immature thymocytes, these cytokines increased viral load.
Cytokines such as IL-2 and IFN-gamma maintain immature thymocytes without increasing viral load and may be useful as adjuncts to improve immune reconstitution after HIV infection.
细胞因子在胸腺细胞分化为成熟T细胞的过程中发挥重要作用；因此，某些细胞因子可能有助于HIV感染后的免疫重建，同时不会增加病毒载量。
研究细胞因子是否会影响植入人胎儿胸腺和肝脏（thy/liv）组织的SCID-hu小鼠感染嗜亲环素蛋白4（CXCR4）型毒株HIV后所导致的免疫耗竭。
thy/liv植入物分别接受模拟感染或感染CXCR4型分子克隆HIV-1 NL4-3。在感染后的第二和第三周，给小鼠注射白细胞介素（IL）-2、IL-4、IL-7、γ干扰素（IFN-γ）或稀释剂。测定胸腺细胞中的病毒载量和免疫表型。
感染后3周时，胸腺细胞亚群分布受到某些细胞因子治疗的显著影响。特别是，IL-2使感染小鼠保留的胸腺细胞谱比用稀释剂处理的感染小鼠更类似于模拟感染小鼠，因为未成熟CD4+CD8+和CD5+CD1+细胞的百分比略高，且变异性远低于用稀释剂处理的感染小鼠。IFN-γ治疗的效果与IL-2相似，但未达到统计学意义。然而，IFN-γ治疗后，成熟CD3+CD69+细胞的百分比保持正常，而在稀释剂处理的感染小鼠中该群体相对增加。虽然IL-4和IL-7治疗延迟了未成熟胸腺细胞的耗竭，但这些细胞因子增加了病毒载量。
IL-2和IFN-γ等细胞因子可维持未成熟胸腺细胞，且不增加病毒载量，可能有助于改善HIV感染后的免疫重建。
