Veazey R S, Mansfield K G, Tham I C, Carville A C, Shvetz D E, Forand A E, Lackner A A
Division of Pathology, New England Regional Primate Research Center, Harvard Medical School, Southborough, Massachusetts 01772, USA.
J Virol. 2000 Dec;74(23):11001-7. doi: 10.1128/jvi.74.23.11001-11007.2000.
Early viral replication and profound CD4(+) T-cell depletion occur preferentially in intestinal tissues of macaques infected with simian immunodeficiency virus (SIV). Here we show that a much higher percentage of CD4(+) T cells in the intestine express CCR5 compared with those found in the peripheral blood, spleen, or lymph nodes. In addition, the selectivity and extent of the CD4(+) T-cell loss in SIV infection may depend upon these cells coexpressing CCR5 and having a "memory" phenotype (CD45RA(-)). Following intravenous infection with SIVmac251, memory CD4(+) CCR5(+) T cells were selectively eliminated within 14 days in all major lymphoid tissues (intestine, spleen, and lymph nodes). However, the effect on CD4(+) T-cell numbers was most profound in the intestine, where cells of this phenotype predominate. The CD4(+) T cells that remain after 14 days of infection lacked CCR5 and/or were naive (CD45RA(+)). Furthermore, when animals in the terminal stages of SIV infection (with AIDS) were examined, virtually no CCR5-expressing CD4(+) T cells were found in lymphoid tissues, and all of the remaining CD4(+) T cells were naive and coexpressed CXCR4. These findings suggest that chemokine receptor usage determines which cells are targeted for SIV infection and elimination in vivo.
早期病毒复制和严重的CD4(+) T细胞耗竭优先发生在感染猴免疫缺陷病毒（SIV）的猕猴肠道组织中。我们在此表明，与外周血、脾脏或淋巴结中的CD4(+) T细胞相比，肠道中表达CCR5的CD4(+) T细胞比例要高得多。此外，SIV感染中CD4(+) T细胞损失的选择性和程度可能取决于这些细胞同时表达CCR5并具有“记忆”表型（CD45RA(-)）。静脉注射SIVmac251后，记忆性CD4(+) CCR5(+) T细胞在14天内在所有主要淋巴组织（肠道、脾脏和淋巴结）中被选择性清除。然而，对CD4(+) T细胞数量的影响在肠道中最为显著，该表型的细胞在肠道中占主导地位。感染14天后剩余的CD4(+) T细胞缺乏CCR5和/或为初始型（CD45RA(+)）。此外，当检查处于SIV感染末期（患艾滋病）的动物时，在淋巴组织中几乎未发现表达CCR5的CD4(+) T细胞，所有剩余的CD4(+) T细胞均为初始型且同时表达CXCR4。这些发现表明趋化因子受体的使用决定了体内哪些细胞成为SIV感染和清除的靶标。
