Disruption of intestinal CD4+ T cell homeostasis is a key marker of systemic CD4+ T cell activation in HIV-infected individuals.
Disruption of intestinal CD4+ T cell homeostasis is a key marker of systemic CD4+ T cell activation in HIV-infected individuals.
复制标题
DOI：
10.4049/jimmunol.1001801
复制
发表时间：
2010-11-01
期刊：
影响因子：
--
通讯作者：
Silvestri G
中科院分区：
文献类型：
--
作者：
Gordon SN;Cervasi B;Odorizzi P;Silverman R;Aberra F;Ginsberg G;Estes JD;Paiardini M;Frank I;Silvestri G
HIV感染与肠道CD4+T细胞耗尽有关，导致粘膜免疫功能障碍、微生物易位、慢性免疫激活和进行性免疫缺陷。在这项研究中，我们检查了病毒复制活跃的HIV感染者(n=15)、接受抗逆转录病毒治疗的患者(n=13)和健康对照组(n=11)，并对来自血液和四个胃肠道(GI)部位(末端回肠、右半结肠、左半结肠和乙状结肠)的T细胞进行了比较分析。正如预期的那样，我们发现HIV感染与所有胃肠道部位的总CD4+T细胞和CD4+CCR5+T细胞的耗尽有关，在接受ART治疗的患者中发现的这些细胞水平高于病毒复制活跃的患者。虽然未经治疗的HIV感染者血液中的CD4+和CD8+T细胞的增殖水平都较高，但同一患者的肠道中只有CD4+T细胞的增殖显著增加。我们还注意到，在血液和肠道组织中，CD4+T细胞的水平和CD4+Ki67+增殖T细胞的百分比呈负相关，因此，在这些不同的解剖分区中，CD4+T细胞的稳态同样受到HIV感染的影响。重要的是，肠道中的CD4+T细胞(包括总细胞和Th17细胞)水平与循环中的CD4+Ki67+T细胞的百分比呈负相关。总而言之，这些数据证实了胃肠道在HIV感染的免疫病理机制中起着关键作用，它们揭示了肠道内CD4+T细胞动态平衡的破坏与全身CD4+T细胞激活水平之间的强烈关联。
HIV infection is associated with depletion of intestinal CD4+ T cells, resulting in mucosal immune dysfunction, microbial translocation, chronic immune activation, and progressive immunodeficiency. In this study, we examined HIV-infected individuals with active virus replication (n = 15), treated with antiretroviral therapy (n = 13), and healthy controls (n = 11) and conducted a comparative analysis of T cells derived from blood and four gastrointestinal (GI) sites (terminal ileum, right colon, left colon, and sigmoid colon). As expected, we found that HIV infection is associated with depletion of total CD4+ T cells as well as CD4+ CCR5+ T cells in all GI sites, with higher levels of these cells found in ART-treated individuals than in those with active virus replication. While the levels of both CD4+ and CD8+ T cell proliferation were higher in the blood of untreated HIV-infected individuals, only CD4+ T cell proliferation was significantly increased in the gut of the same patients. We also noted that the levels of CD4+ T cells and the percentages of CD4+Ki67+ proliferating T cells are inversely correlated in both blood and intestinal tissues, thus suggesting that CD4+ T cell homeostasis is similarly affected by HIV infection in these distinct anatomic compartments. Importantly, the level of intestinal CD4+ T cells (both total and Th17 cells) was inversely correlated with the percentage of circulating CD4+Ki67+ T cells. Collectively, these data confirm that the GI tract is a key player in the immunopathogenesis of HIV infection, and they reveal a strong association between the destruction of intestinal CD4+ T cell homeostasis in the gut and the level of systemic CD4+ T cell activation.
登录
查看更多内容
影响因子：
20.3
作者：
Deeks, SG;Kitchen, CMR;Hecht, FM
通讯作者：
Hecht, FM
影响因子：
5.4
作者：
Fukazawa, Yoshinori;Miyake, Ariko;Miura, Tomoyuki
通讯作者：
Miura, Tomoyuki
DOI：
10.1084/jem.20041196
发表时间：
2004-09-20
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Mehandru S;Poles MA;Tenner-Racz K;Horowitz A;Hurley A;Hogan C;Boden D;Racz P;Markowitz M
通讯作者：
Markowitz M
影响因子：
64.8
作者：
Li, QS;Duan, LJ;Haase, AT
通讯作者：
Haase, AT
影响因子：
8
作者：
Ciccone, E. J.;Read, S. W.;Sereti, I.
通讯作者：
Sereti, I.