Hou S, Doherty P C, Zijlstra M, Jaenisch R, Katz J M
Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105.
J Immunol. 1992 Aug 15;149(4):1319-25.
The role and interdependence of CD8+ and CD4+ alpha beta-T cells in the acute response after respiratory infection with the murine parainfluenza type 1 virus, Sendai virus, has been analyzed for H-2b mice. Enrichment of CD8+ virus-specific CTL effectors in the lungs of immunologically intact C57BL/6 animals coincided with the clearance of the virus from this site by day 10 after infection. Removal of the CD4+ T cells by in vivo mAb treatment did not affect appreciably either the recruitment of CD8+ T cells to the infected lung, or their development into virus-specific cytotoxic effectors. In contrast, depletion of the CD8+ subset delayed virus clearance, although most mice survived the infection. Transgenic H-2b F3 mice homozygous (-/-) for a beta 2 microglobulin (beta 2-m) gene disruption, which lack both class I MHC glycoproteins and mature CD8+ alpha beta-T cells, showed a comparable, delayed clearance of Sendai virus from the lung. Virus-specific, class II MHC-restricted CTL were demonstrated in both freshly isolated bronchoalveolar lavage populations and cultured lymph node and spleen tissue from the beta 2-m (-/-) transgenics. Treatment of the beta 2-m (-/-) mice with the mAb to CD4 led to delayed virus clearance and death, which was also the case for normal mice that were depleted simultaneously of the CD4+ and CD8+ subsets. These results indicate that, although classical class I MHC-restricted CD8+ cytotoxic T cells normally play a dominant role in the recovery of mice acutely infected with Sendai virus, alternative mechanisms involving CD4+ T cells exist and can compensate, in time, for the loss of CD8+ T cell function.
对于H-2b小鼠，已分析了CD8⁺和CD4⁺αβ-T细胞在感染鼠1型副流感病毒（仙台病毒）后的急性反应中的作用及相互依赖性。在免疫健全的C57BL/6动物的肺中，CD8⁺病毒特异性CTL效应细胞的富集与感染后第10天该部位病毒的清除同时发生。通过体内单克隆抗体处理去除CD4⁺T细胞，对CD8⁺T细胞向感染肺的募集或其发育为病毒特异性细胞毒性效应细胞均无明显影响。相反，CD8⁺亚群的耗竭延迟了病毒清除，尽管大多数小鼠在感染中存活下来。β2微球蛋白（β2-m）基因缺失的纯合（-/-）转基因H-2b F3小鼠缺乏I类MHC糖蛋白和成熟的CD8⁺αβ-T细胞，其肺中仙台病毒的清除也出现类似的延迟。在新鲜分离的支气管肺泡灌洗细胞群体以及来自β2-m（-/-）转基因小鼠的培养淋巴结和脾脏组织中均证实了病毒特异性、II类MHC限制性CTL。用抗CD4单克隆抗体处理β2-m（-/-）小鼠导致病毒清除延迟和死亡，同时去除CD4⁺和CD8⁺亚群的正常小鼠也出现这种情况。这些结果表明，虽然经典的I类MHC限制性CD8⁺细胞毒性T细胞通常在急性感染仙台病毒的小鼠恢复中起主导作用，但涉及CD4⁺T细胞的替代机制存在，并且可以及时补偿CD8⁺T细胞功能的丧失。
