Severe depletion of CD4+ CD25+ regulatory T cells from the intestinal lamina propria but not peripheral blood or lymph nodes during acute simian immunodeficiency virus infection
Severe depletion of CD4+ CD25+ regulatory T cells from the intestinal lamina propria but not peripheral blood or lymph nodes during acute simian immunodeficiency virus infection
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DOI：
10.1128/jvi.00841-07
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发表时间：
2007-12-01
影响因子：
5.4
通讯作者：
Siliciano, Robert F.
中科院分区：
文献类型：
--
作者：
Chase, Amanda J.;Sedaghat, Ahmad R.;Siliciano, Robert F.
CD 4（+）CD 25（+）调节性T细胞（Treg）抑制效应淋巴细胞的活化和增殖。在人类免疫缺陷病毒1型（HIV-1）感染中，TcR在控制未感染的CD 4（+）T细胞的凋亡丢失方面发挥重要作用，这些细胞是由高水平的全身免疫激活引起的。在急性HIV-1感染期间，超过50%的CD 4（+）T细胞从胃肠道固有层中耗尽。为了阐明Tcl 4在HIV-1诱导的肠道相关淋巴组织（GALT）中CD 4（+）T细胞耗竭中的作用，我们首先使用猴免疫缺陷病毒（SIV）/猪尾猕猴HIV-1疾病模型确定Tcl 4在急性感染环境中的分布。在接种后第4、14和114天，从SIV感染的短尾猕猴的GALT、淋巴结和外周血中分离CD 4（+）T细胞。实时定量逆转录PCR用于定量SIV感染和未感染对照猕猴中FOXP 3的拷贝数。FOXP 3在回肠固有层中的表达在感染的所有阶段与未感染的对照猕猴中的水平相比显著降低。此外，对SIV感染猕猴回肠CD 4（+）T细胞的功能分析显示，该细胞缺乏抑制活性，这表明该区域内没有TcR。这些结果表明，Treg在SIV感染的猕猴的GALT中迅速耗尽，定义了在疾病发病机制的早期事件中Treg介导的抑制的丧失的作用。
CD4(+) CD25(+) regulatory T cells (Tregs) suppress the activation and proliferation of effector lymphocytes. In human immunodeficiency virus type 1 (HIV-1) infection, Tregs play a significant role in controlling the apoptotic loss of uninfected CD4(+) T cells resulting from high levels of generalized immune activation. During acute HIV-1 infection, more than 50% of CD4(+) T cells are depleted from the gastrointestinal lamina propria. To elucidate the role of Tregs in HIV-1-induced depletion of CD4(+) T cells in the gut-associated lymphoid tissue (GALT), we first determine the distribution of Tregs in a setting of acute infection using the simian immunodeficiency virus (SIV)/pigtailed macaque model of HIV-1 disease. CD4(+) T cells from the GALT, lymph nodes, and peripheral blood were isolated from SIV-infected pigtailed macaques on days 4, 14, and 114 postinoculation. Quantitative real-time reverse transcription-PCR was used to quantitate FOXP3 copy numbers in SIV-infected and uninfected control macaques. Expression of FOXP3 in the ileal lamina propria was significantly decreased at all stages of infection compared to levels in uninfected control macaques. In addition, functional analysis of ileal CD4(+) T cells from SIV-infected macaques revealed a lack of suppressive activity suggestive of the absence of Tregs in that compartment. These results indicate that Tregs are rapidly depleted in the GALT of SIV-infected macaques, defining a role for the loss of Treg-mediated suppression in early events in the pathogenesis of the disease.