Stohlman S A, Bergmann C C, Lin M T, Cua D J, Hinton D R
Department of Neurology, University of Southern California, Los Angeles 90033, USA.
J Immunol. 1998 Mar 15;160(6):2896-904.
CTL responses induced during most viral infections are independent of help derived from the CD4+ T cell population. However, clearance of virus from the central nervous system (CNS) during infection with the neurotropic JHM strain of mouse hepatitis virus is inhibited in the absence of CD4+ T cells. Adoptive transfer of activated CD8+ T cells with virus-specific cytolytic activity into CD4+ T cell-depleted hosts demonstrated that CD4+ T cells were one component of the host response required for expression of CTL effector function(s) within the CNS. Analysis of mice infected with the JHM strain of mouse hepatitis virus demonstrated that, in contrast to CD8+ T cells, few CD4+ T cells entered the brain parenchyma. Although fewer CD8+ T cells entered the brain parenchyma in mice depleted of CD4+ T cells, access of CTL was not inhibited in the absence of CD4+ T cells. The number of apoptotic lymphocytes in the CNS increased in the absence of CD4+ T cells, suggesting that CTL enter the CNS during viral infection in a CD4-independent manner. However, these cells rapidly undergo apoptosis, indicating that expression of CTL effector function with the parenchyma of the CNS is CD4 dependent. These data raise the possibility that programmed cell death of CD8+ T cells within the CNS is due to the increased Ag present in the CNS of infected CD4 depleted mice or that autocrine cytokines, which maintain CTL activity within peripheral tissues, are inhibited in the microenvironment of the CNS.
在大多数病毒感染期间诱导产生的细胞毒性T淋巴细胞（CTL）反应不依赖于来自CD4 + T细胞群体的辅助。然而，在感染嗜神经性小鼠肝炎病毒JHM株的过程中，若没有CD4 + T细胞，病毒从中枢神经系统（CNS）的清除会受到抑制。将具有病毒特异性细胞溶解活性的活化CD8 + T细胞过继转移到CD4 + T细胞耗竭的宿主中，结果表明CD4 + T细胞是CNS内CTL效应功能表达所需的宿主反应的一个组成部分。对感染小鼠肝炎病毒JHM株的小鼠进行分析表明，与CD8 + T细胞不同，很少有CD4 + T细胞进入脑实质。虽然在CD4 + T细胞耗竭的小鼠中进入脑实质的CD8 + T细胞较少，但在没有CD4 + T细胞的情况下CTL的进入并未受到抑制。在没有CD4 + T细胞的情况下，CNS中凋亡淋巴细胞的数量增加，这表明CTL在病毒感染期间以不依赖CD4的方式进入CNS。然而，这些细胞迅速发生凋亡，这表明CTL效应功能在CNS实质中的表达是依赖CD4的。这些数据提出了一种可能性，即CNS内CD8 + T细胞的程序性细胞死亡是由于感染的CD4耗竭小鼠的CNS中存在的抗原增加，或者是由于维持外周组织中CTL活性的自分泌细胞因子在CNS的微环境中受到抑制。
