Profound CD4+/CCR5+ T cell expansion is induced by CD8+ lymphocyte depletion but does not account for accelerated SIV pathogenesis.
Profound CD4+/CCR5+ T cell expansion is induced by CD8+ lymphocyte depletion but does not account for accelerated SIV pathogenesis.
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DOI：
10.1084/jem.20090356
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发表时间：
2009-07-06
期刊：
影响因子：
--
通讯作者：
Picker LJ
中科院分区：
文献类型：
--
作者：
Okoye A;Park H;Rohankhedkar M;Coyne-Johnson L;Lum R;Walker JM;Planer SL;Legasse AW;Sylwester AW;Piatak M Jr;Lifson JD;Sodora DL;Villinger F;Axthelm MK;Schmitz JE;Picker LJ
急性猴免疫缺陷病毒(SIV)感染猕猴(RMS)过程中CD8+淋巴细胞的耗竭导致病毒复制高峰不可逆转的延长和疾病的快速进展，这与CD8+淋巴细胞在确定急性期后病毒复制设定点中的主要作用是一致的。然而，我们报告CD8+淋巴细胞耗竭也与CD4+效应记忆T细胞(TEM)和过渡性记忆T(TTrM)细胞(程度较小)的增殖显著相关，这提出了一个问题，即最佳(激活/增殖)、CD4+/CCR5+SIV“靶细胞”的可用性增加是否有助于这种加速的发病。与此相一致，SIVCD8RMS中CD8+淋巴细胞的耗尽导致潜在−+SIV靶细胞数量的持续增加，而在急性SIV感染中，这种耗尽导致靶细胞消耗增加。然而，我们发现CD8+淋巴细胞耗竭的、急性SIV感染的RMS的过度的CD4+TEM细胞增殖可被白介素15中和完全抑制，并且这种抑制并不能消除这些RMS中快速进展的感染。此外，尽管在急性感染期间应用IL-15可诱导强劲的CD4+T细胞和TTrM细胞增殖，但它不能概括CD8+淋巴细胞耗尽的病毒动力学。这些数据表明，CD8+淋巴细胞功能对急性SIV感染结局的影响大于可用于感染和病毒产生的靶细胞的数量和/或激活状态。
Depletion of CD8+ lymphocytes during acute simian immunodeficiency virus (SIV) infection of rhesus macaques (RMs) results in irreversible prolongation of peak-level viral replication and rapid disease progression, consistent with a major role for CD8+ lymphocytes in determining postacute-phase viral replication set points. However, we report that CD8+ lymphocyte depletion is also associated with a dramatic induction of proliferation among CD4+ effector memory T (TEM) cells and, to a lesser extent, transitional memory T (TTrM) cells, raising the question of whether an increased availability of optimal (activated/proliferating), CD4+/CCR5+ SIV “target” cells contributes to this accelerated pathogenesis. In keeping with this, depletion of CD8+ lymphocytes in SIV− RMs led to a sustained increase in the number of potential CD4+ SIV targets, whereas such depletion in acute SIV infection led to increased target cell consumption. However, we found that the excess CD4+ TEM cell proliferation of CD8+ lymphocyte–depleted, acutely SIV-infected RMs was completely inhibited by interleukin (IL)-15 neutralization, and that this inhibition did not abrogate the rapidly progressive infection in these RMs. Moreover, although administration of IL-15 during acute infection induced robust CD4+ TEM and TTrM cell proliferation, it did not recapitulate the viral dynamics of CD8+ lymphocyte depletion. These data suggest that CD8+ lymphocyte function has a larger impact on the outcome of acute SIV infection than the number and/or activation status of target cells available for infection and viral production.
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影响因子：
4.4
作者：
Cecchinato, Valentina;Tryniszewska, Elzbieta;Franchini, Genoveffa
通讯作者：
Franchini, Genoveffa
影响因子：
0.7
作者：
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通讯作者：
Ansari, AA
影响因子：
5.4
作者：
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Hirsch, VM
影响因子：
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作者：
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通讯作者：
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影响因子：
64.8
作者：
Barouch, DH;Kunstman, J;Letvin, NL
通讯作者：
Letvin, NL