Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston MA 02215, USA.
J Infect Dis. 2013 Oct 1;208(7):1113-22. doi: 10.1093/infdis/jit249. Epub 2013 Jun 6.
Human immunodeficiency virus type 1 (HIV-1) infection is associated with a massive depletion of intestinal CD4(+) T cells that is only partially reversed by combination antiretroviral therapy (cART). Here, we assessed the ability of nucleoside reverse-transcriptase inhibitor/nonnucleoside reverse-transcriptase inhibitor treatment to restore the CD4(+) T-cell populations in the intestine of South African patients with AIDS.
Thirty-eight patients with advanced HIV-1 infection who had chronic diarrhea (duration, >4 weeks) and/or unintentional weight loss (>10% decrease from baseline) of uncertain etiology were enrolled. Blood specimens were collected monthly, and gastrointestinal tract biopsy specimens were collected before cART initiation (from the duodenum, jejunum, ileum, and colon), 3 months after cART initiation (from the duodenum), and 6 months after cART initiation (from the duodenum and colon). CD4(+), CD8(+), and CD38(+)CD8(+) T cells were quantified by flow cytometry and immunohistochemistry analyses, and the HIV-1 RNA load was determined by the Nuclisens assay.
CD4(+) T-cell and HIV-1 RNA levels were significantly lower, whereas CD8(+) T-cell levels, including activated CD38(+)CD8(+) T cell levels, were higher in the duodenum and jejunum, compared with the colon. After 6 months of cART, a significant but incomplete recovery of CD4(+) T cells was detected in the colon and peripheral blood but not in the duodenum. Failed restoration of the CD4(+) T-cell count in the duodenum was associated with nonspecific enteritis and CD8(+) T-cell activation.
Strategies that target inflammation and immune activation in the small intestine may be required to expedite CD4(+) T-cell recovery and improve therapeutic outcomes.
人类免疫缺陷病毒 1 型（HIV-1）感染会导致肠道 CD4(+)T 细胞大量耗竭，这种耗竭仅部分通过联合抗逆转录病毒治疗（cART）得到逆转。在这里，我们评估了核苷逆转录酶抑制剂/非核苷逆转录酶抑制剂治疗恢复南非艾滋病患者肠道 CD4(+)T 细胞群体的能力。
38 名患有晚期 HIV-1 感染的患者患有慢性腹泻（持续时间>4 周）和/或原因不明的非自愿体重减轻（基线下降>10%）。每月采集血液标本，在开始 cART 前（十二指肠、空肠、回肠和结肠）、开始 cART 后 3 个月（十二指肠）和开始 cART 后 6 个月（十二指肠和结肠）采集胃肠道活检标本。通过流式细胞术和免疫组织化学分析定量 CD4(+)、CD8(+)和 CD38(+)CD8(+)T 细胞，并通过 Nuclisens 检测法确定 HIV-1 RNA 载量。
与结肠相比，十二指肠和空肠中的 CD4(+)T 细胞和 HIV-1 RNA 水平显著降低，而 CD8(+)T 细胞水平，包括激活的 CD38(+)CD8(+)T 细胞水平升高。在 cART 治疗 6 个月后，在结肠和外周血中观察到 CD4(+)T 细胞的显著但不完全恢复，但在十二指肠中未观察到。十二指肠 CD4(+)T 细胞计数恢复失败与非特异性肠炎和 CD8(+)T 细胞激活有关。
可能需要针对小肠炎症和免疫激活的策略来加快 CD4(+)T 细胞恢复并改善治疗结果。
