Immunosuppression by CD4+ regulatory T cells induced by chronic retroviral infection
Immunosuppression by CD4+ regulatory T cells induced by chronic retroviral infection
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DOI：
10.1073/pnas.151174198
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发表时间：
2001-07-31
影响因子：
11.1
通讯作者：
Hasenkrug, KJ
中科院分区：
文献类型：
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作者：
Iwashiro, M;Messer, RJ;Hasenkrug, KJ
正常水平的CD 4（+）调节性T细胞对于维持免疫稳态和预防自身免疫性疾病至关重要。然而，我们现在发现，CD 4（+）调节性T细胞对慢性病毒感染的反应扩增可导致免疫抑制。持续感染Friend逆转录病毒的小鼠，其脾脏CD 4（+）调节性T细胞的比例大约是正常的两倍，并丧失了对某些肿瘤移植物的排斥能力。CD 4（+）调节性T细胞的作用通过过继转移CD 4（+）T细胞将免疫抑制传递给未感染的小鼠来证明。来自慢性感染小鼠的CD 4（+）T细胞在体外也具有免疫抑制作用，抑制混合淋巴细胞培养物中溶细胞性T淋巴细胞的产生。通过涉及转化生长因子-β和细胞表面分子CTLA-4（CD 152）的一种或多种机制，在胚细胞形成水平上发生抑制。这些结果表明，在T细胞耗竭的情况下，HIV和人T细胞白血病病毒-I诱导的免疫抑制可能是一种解释。
Normal levels of CD4(+) regulatory T cells are critical for the maintenance of immunological homeostasis and the prevention of autoimmune diseases. However, we now show that the expansion of CD4(+) regulatory T cells in response to a chronic viral infection can lead to immunosuppression. Mice persistently infected with Friend retrovirus develop approximately twice the normal percentage of splenic CD4(+) regulatory T cells and lose their ability to reject certain tumor transplants. The role of CD4(+) regulatory T cells was demonstrated by the transmission of immunosuppression to uninfected mice by adoptive transfers of CD4(+) T cells. CD4(+) T cells from chronically infected mice were also immunosuppressive in vitro, inhibiting the generation of cytolytic T lymphocytes in mixed lymphocyte cultures. Inhibition occurred at the level of blast-cell formation through a mechanism or mechanisms involving transforming growth factor-beta and the cell surface molecule CTLA-4 (CD152). These results suggest a possible explanation for HIV- and human T cell leukemia virus-I-induced immunosuppression in the absence of T cell depletion.