Lightman S, Cobbold S, Waldmann H, Askonas B A
Division of Immunology, National Institute for Medical Research, Mill Hill, London, U.K.
Immunology. 1987 Sep;62(1):139-44.
This study aimed to analyse the roles of Lyt 2+ and L3T4+ memory T-cell subpopulations in murine influenza infection. Previous work has shown that Lyt 2+ cytotoxic T-cell (Tc) clones can adoptively transfer protection. We therefore wished to see whether L3T4+ (Th) cells could also act as protective effector cells. Donors for adoptive cell transfer were thymectomized mice, depleted in vivo of either Lyt 2+ or L3T4+ T cells with monoclonal antibodies (MAb) and then infected with influenza virus (A/X31). Primed spleen cells, after removal of the B cells, were transferred into irradiated hosts infected simultaneously or persistently with a heterologous influenza virus and the effect on lung virus replication determined. Depletion of L3T4+ T cells suppressed the formation of IgG antibodies after influenza virus infection, indicating significant depletion of T-helper function. Yet Lyt 2+ class I MHC-restricted Tc cells were effectively primed in these mice, albeit to half the normal level. Adoptive transfer of the Lyt 2+ memory T cells cleared virus in a persistent infection within 6 days. Spleen cells selected for L3T4+ T cells cleared virus within 21 days of transfer in a simultaneous infection and reduced viral titres in a persistent infection, but not as effectively as L3T4+-depleted spleen cells. Although no Lyt 2+ cells were detected by fluorescence staining in Lyt 2+-depleted spleens, we could detect low levels of class I MHC-restricted influenza-specific Tc memory cells in host spleens following influenza infection. Therefore, whether the early viral clearance is solely due to L3T4+ T cells is not clear. Lyt 2+ memory T cells appear more efficient in this respect than L3T4+ memory T cells.
本研究旨在分析Lyt 2⁺和L3T4⁺记忆性T细胞亚群在小鼠流感感染中的作用。先前的研究表明，Lyt 2⁺细胞毒性T细胞（Tc）克隆可通过过继转移提供保护作用。因此，我们想了解L3T4⁺（Th）细胞是否也能作为保护性效应细胞。用于过继细胞转移的供体是胸腺切除的小鼠，用单克隆抗体（MAb）在体内清除Lyt 2⁺或L3T4⁺ T细胞，然后感染流感病毒（A/X31）。去除B细胞后的致敏脾细胞被转移到同时或持续感染异源流感病毒的受照射宿主中，并测定其对肺病毒复制的影响。L3T4⁺ T细胞的清除抑制了流感病毒感染后IgG抗体的形成，表明T辅助功能显著耗竭。然而，Lyt 2⁺ I类MHC限制性Tc细胞在这些小鼠中仍能有效致敏，尽管水平只有正常水平的一半。Lyt 2⁺记忆性T细胞的过继转移在6天内清除了持续性感染中的病毒。选择L3T4⁺ T细胞的脾细胞在同时感染后21天内清除了病毒，并在持续性感染中降低了病毒滴度，但效果不如耗尽L3T4⁺的脾细胞。尽管在耗尽Lyt 2⁺的脾脏中通过荧光染色未检测到Lyt 2⁺细胞，但我们在流感感染后的宿主脾脏中检测到了低水平的I类MHC限制性流感特异性Tc记忆细胞。因此，早期病毒清除是否仅归因于L3T4⁺ T细胞尚不清楚。在这方面，Lyt 2⁺记忆性T细胞似乎比L3T4⁺记忆性T细胞更有效。
