Hogan R J, Zhong W, Usherwood E J, Cookenham T, Roberts A D, Woodland D L
Trudeau Institute, Saranac Lake, New York 12983, USA.
J Exp Med. 2001 Apr 16;193(8):981-6. doi: 10.1084/jem.193.8.981.
Although CD4(+) T cells have been shown to mediate protective cellular immunity against respiratory virus infections, the underlying mechanisms are poorly understood. For example, although phenotypically distinct populations of memory CD4(+) T cells have been identified in different secondary lymphoid tissues, it is not known which subpopulations mediate protective cellular immunity. In this report, we demonstrate that virus-specific CD4(+) T cells persist in the lung tissues and airways for several months after Sendai virus infection of C57BL/6 mice. A large proportion of these cells possess a highly activated phenotype (CD44(hi), CD62L(lo), CD43(hi), and CD25(hi)) and express immediate effector function as indicated by the production of interferon gamma after a 5-h restimulation in vitro. Furthermore, intratracheal adoptive transfer of lung memory cells into beta2m-deficient mice demonstrated that lung-resident virus-specific CD4(+) T cells mediated a substantial degree of protection against secondary virus infection. Taken together, these data demonstrate that activated memory CD4(+) T cells persisting at mucosal sites play a critical role in mediating protective cellular immunity.
尽管已证明CD4(+) T细胞介导针对呼吸道病毒感染的保护性细胞免疫，但其潜在机制仍知之甚少。例如，尽管在不同的二级淋巴组织中已鉴定出表型不同的记忆CD4(+) T细胞群体，但尚不清楚哪些亚群介导保护性细胞免疫。在本报告中，我们证明，仙台病毒感染C57BL/6小鼠后，病毒特异性CD4(+) T细胞在肺组织和气道中持续存在数月。这些细胞中的很大一部分具有高度活化的表型（CD44(hi)、CD62L(lo)、CD43(hi)和CD25(hi)），并且在体外再刺激5小时后通过产生干扰素γ表明具有即时效应功能。此外，将肺记忆细胞经气管内过继转移至β2m缺陷小鼠表明，肺驻留病毒特异性CD4(+) T细胞介导了对继发性病毒感染的显著程度的保护。综上所述，这些数据表明，在粘膜部位持续存在的活化记忆CD4(+) T细胞在介导保护性细胞免疫中起关键作用。
