Talal A H, Monard S, Vesanen M, Zheng Z, Hurley A, Cao Y, Fang F, Smiley L, Johnson J, Kost R, Markowitz M H
Aaron Diamond AIDS Research Center, New York City, New York, USA.
J Acquir Immune Defic Syndr. 2001 Jan 1;26(1):1-7. doi: 10.1097/00126334-200101010-00001.
We evaluated virologic and immunologic responses to antiretroviral therapy in gut-associated lymphoid tissue (GALT) compared with those found in peripheral blood.
Eight HIV-1-infected individuals were treated with three reverse transcriptase inhibitors and one protease inhibitor. Endoscopic biopsies were performed at baseline, and at months 1, 2, and 6. We measured the level of cell-associated multiply spliced and unspliced HIV-1 mRNA in GALT and in peripheral blood mononuclear cells. Immunologic responses were assessed by flow cytometry.
Levels of multiply spliced HIV-1 mRNA declined in parallel fashion both in peripheral blood and GALT. After 6 months of therapy, unspliced HIV-1 mRNA in the GALT was below assay detection although it persisted in peripheral blood mononuclear cells in 4 study subjects. Although the percentage of CD4+ lymphocytes increased significantly in peripheral blood, only modest increases occurred in GALT. The percentage of activated CD8+ T cells decreased significantly in peripheral blood whereas only modest reductions occurred in GALT.
Antiretroviral therapy effectively suppressed HIV-1 replication in GALT. The percentage of CD4+ T cells in peripheral blood uniformly increased in all study subjects, whereas it was more variable in the GALT.
我们评估了肠道相关淋巴组织(GALT)对抗逆转录病毒疗法的病毒学和免疫学反应,并与外周血中的反应进行了比较。
8名HIV-1感染者接受了三种逆转录酶抑制剂和一种蛋白酶抑制剂的治疗。在基线时以及第1、2和6个月进行了内镜活检。我们测量了GALT和外周血单核细胞中与细胞相关的多重剪接和未剪接HIV-1 mRNA的水平。通过流式细胞术评估免疫反应。
外周血和GALT中多重剪接HIV-1 mRNA的水平以平行方式下降。治疗6个月后,GALT中未剪接的HIV-1 mRNA低于检测水平,尽管在4名研究对象的外周血单核细胞中仍然存在。虽然外周血中CD4 +淋巴细胞的百分比显著增加,但GALT中仅出现适度增加。外周血中活化CD8 + T细胞的百分比显著下降,而GALT中仅出现适度降低。
抗逆转录病毒疗法有效地抑制了GALT中的HIV-1复制。所有研究对象外周血中CD4 + T细胞的百分比均一致增加,而GALT中的变化更大。