The CD4 molecule on CD8+ T lymphocytes directly enhances the immune response to viral, and cellular antigens
The CD4 molecule on CD8+ T lymphocytes directly enhances the immune response to viral, and cellular antigens
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DOI：
10.1073/pnas.0406603102
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发表时间：
2005-03-08
影响因子：
11.1
通讯作者：
Zack, JA
中科院分区：
文献类型：
--
作者：
Kitchen, SG;Whitmire, JK;Zack, JA
CD8(+)T淋巴细胞在外源抗原的细胞免疫应答中起重要作用。我们之前已经证明，共刺激纯化的人CD8(+)T细胞可以诱导CD4分子的从头表达，并且在体外，CD4与这种细胞类型的连接可以调节CD8(+)T细胞的活性。在这里，我们通过将CD8基因敲除小鼠的CD8细胞过继转移到严重联合免疫缺陷(SCID)受者体内，研究了小鼠CD8(+)T细胞上表达的CD4分子如何在体内促进CD8(+)细胞的反应。将这些细胞转移到同基因的SCID小鼠中，导致了对淋巴细胞性脉络膜脑膜炎病毒感染的免疫反应降低。即使在存在CD4(+)T细胞的情况下，这些反应也会降低，这表明这确实是CD8细胞缺陷。类似地，将不能表达CD4的CD8(+)T细胞转移到同种异体SCID小鼠中，与正常CD8(+)T细胞相比，对同种异体抗原的反应性降低。因此，CD8T淋巴细胞上的CD4表达调节细胞毒性T淋巴细胞的功能，在体内对病毒和同种异体抗原的最佳细胞免疫至关重要。
CD8(+) T lymphocytes play a major role in cellular-mediated immune responses to foreign antigen. We have previously demonstrated that costimulation of purified human CD8(+) T cells induces de novo expression of the CD4 molecule and that ligation of CD4 on this cell type modulates CD8(+) T cell activity in vitro. Herein, we investigate how the CD4 molecule expressed on murine CD8(+) T cells contributes to CD8(+) cell responses in vivo by employing adoptive transfer of CD8 cells from CD4 knockout mice into severe combined immunodeficient (SCID) recipients. Transfer of these cells into syngeneic SCID mice resulted in a decreased immune response to infection by lymphocytic choriomeningitis virus. These decreased responses occurred even in the presence of CD4(+) T cells, indicating that this was truly a CD8-cell defect. Similarly, transfer of CD8(+) T cells incapable of expressing CD4 into allogeneic SCID mice resulted in a decreased response to alloantigens compared with that of normal CD8(+) T cells. Therefore, CD4 expression on CD8 T lymphocytes modulates cytotoxic T lymphocyte function and is critical in vivo for optimal cell-mediated immunity to viral and alloantigens.