HIV-1-specific CTLs effectively suppress replication of HIV-1 in HIV-1-infected macrophages
HIV-1-specific CTLs effectively suppress replication of HIV-1 in HIV-1-infected macrophages
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DOI：
10.1182/blood-2006-07-037481
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发表时间：
2007-06-01
期刊：
影响因子：
20.3
通讯作者：
Takiguchi, Masafumi
中科院分区：
文献类型：
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作者：
Fujiwara, Mamoru;Takiguchi, Masafumi
CD 4（+）T细胞和巨噬细胞都是HIV-1的主要储存库。以往的研究表明，HIV-1特异性细胞毒性T淋巴细胞（CTL）几乎不识别HIV-1感染的CD 4（+）T细胞，因为Nef介导的HILA I类下调，这表明HIV-1逃避HIV-1特异性CTL，并继续在HIV-1感染的供体中复制。另一方面，HIV-1感染的巨噬细胞的CTL识别和Nef介导的HILA I类下调对这种识别的影响仍然不清楚。我们显示了强烈的HIV-1抗原呈递HIV-1感染的巨噬细胞。HIV-1特异性CTL具有较强的抑制HIV-1 R5病毒在HIV-1感染的巨噬细胞中复制和杀伤HIV-11 R5感染的巨噬细胞的能力。Nef介导的HLA I类下调对HIV-1特异性CTL识别HIV-1感染的巨噬细胞的影响最小。此外，HIV-1感染的巨噬细胞比HIV-1感染的CD 4（+）T细胞具有更强的刺激HIV-1特异性CTL增殖的能力。因此，Nef介导的HLA I类下调对HIV-1感染的巨噬细胞的HIV-1特异性CTL识别的影响不如HIV-1感染的CD 4（+）T细胞。这些发现支持了这样的观点，即HIV-1感染的巨噬细胞的强HIV-1抗原呈递是在HIV-1感染的急性和早期慢性阶段介导有效诱导HIV-1特异性CTL的机制之一。
Both CD4(+) T cells and macrophages are major reservoirs of HIV-1. Previous study showed that HIV-1-specific cytolytic T lymphocytes (CTLs) hardly recognize HIV1-infected CD4(+) T cells because of Nef-mediated HILA class I down-regulation, suggesting that HIV-1 escapes from HIV1-specific CTLs and continues to replicate in HIV-1-infected donors. On the other hand, the CTL recognition of HIV-1-infected macrophages and the effect of Nef-mediated HILA class I down-regulation on this recognition still remain unclear. We show a strong HIV-1 antigen presentation by HIV-1-infected macrophages. HIV-1-specific CTLs had strong abilities to suppress HIV-1R5 virus replication in HIV-1-infected macrophages and to kill HIV-11R5-infected macrophages. Nef-mediated HLA class I down-regulation minimally influenced the recognition of HIV-1-infected macrophages by HIV-1-specific CTLs. In addition, HIV-1-infected macrophages had a stronger ability to stimulate the proliferation of HIV-1-specific CTLs than HIV-1-infected CD4(+) T cells. Thus, the effect of Nef-mediated HLA class I down-regulation was less critical with respect to the recognition by HIV-1-specific CTLs of HIV-Infected macrophages than that of HIV-1-infected CD4(+) T cells. These findings support the idea that the strong HIV-1 antigen presentation by HIV-1-infected macrophages is one of the mechanisms mediating effective induction of HIV-1-specific CTLs in the acute and early chronic phases of HIV-1 infection.