Deckhut A M, Allan W, McMickle A, Eichelberger M, Blackman M A, Doherty P C, Woodland D L
Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105.
J Immunol. 1993 Sep 1;151(5):2658-66.
The spectrum of TCR usage has been analyzed for virus-specific CD8+ T cells isolated from the regional mediastinal lymph modes and from the lung by bronchoalveolar lavage (BAL) of C57BL/6 (B6) mice with influenza pneumonia. Lymphocytes were recovered during the acute phase of the primary response in mice infected with an H3N2 (A/HKx31) virus, or in immune animals that were secondarily challenged with an H1N1 virus (A/PR8). Cells taken directly from the BAL of infected mice exhibited an increase in the frequency of V beta 8.3+/CD8+ T cells. In addition, 20 to 50% of proliferating CD8+ T cells in the mediastinal lymph nodes and BAL populations stimulated in vitro with A/HKx31 were V beta 8.3 TCR+. These observations indicated that the V beta 8.3+/CD8+ T cells were specifically involved in the inflammatory process during influenza infection. However, in vivo depletion of V beta 8+ T cells in CD4-depleted mice did not adversely affect viral clearance, suggesting that other CD8+ T cells can compensate for the absence of these cells. The spectrum of TCR usage was also analyzed for influenza-specific T cell hybridomas derived from freshly isolated BAL of mice with pneumonia. Many of these T cell hybridomas were V beta 8.3+, although other TCR V beta elements were used. All of the V beta 8.3+ hybridomas recognized the H-2Db-restricted NP epitope, 365-380. Although the V beta 8.3 TCR contain similar TCR D beta and J beta elements, V alpha usage was surprisingly variable. Therefore, recognition of this particular epitope was dominated by the beta-chain of the TCR. We conclude that the murine CD8+ response to influenza A virus infection of B6 mice is limited in terms of the diversity of the responding T cells. However, there is significant plasticity in the CD8+ response, which readily compensates for the absence of the dominant T cell population.
对从患有流感肺炎的C57BL/6（B6）小鼠的纵隔局部淋巴结以及通过支气管肺泡灌洗（BAL）从肺中分离出的病毒特异性CD8 + T细胞的TCR使用谱进行了分析。淋巴细胞是在感染H3N2（A/HKx31）病毒的小鼠的初次反应急性期，或在再次受到H1N1病毒（A/PR8）攻击的免疫动物中回收的。直接从感染小鼠的BAL中获取的细胞显示Vβ8.3 + /CD8 + T细胞频率增加。此外，在体外受到A/HKx31刺激的纵隔淋巴结和BAL群体中，20%至50%的增殖性CD8 + T细胞是Vβ8.3 TCR +。这些观察结果表明，Vβ8.3 + /CD8 + T细胞在流感感染期间特异性参与了炎症过程。然而，在CD4缺失的小鼠中体内清除Vβ8 + T细胞并未对病毒清除产生不利影响，这表明其他CD8 + T细胞可以弥补这些细胞的缺失。还对源自患有肺炎的小鼠新鲜分离的BAL的流感特异性T细胞杂交瘤的TCR使用谱进行了分析。这些T细胞杂交瘤中的许多是Vβ8.3 +，尽管也使用了其他TCR Vβ元件。所有Vβ8.3 +杂交瘤都识别H-2Db限制性NP表位，365-380。尽管Vβ8.3 TCR包含相似的TCR Dβ和Jβ元件，但Vα的使用却出人意料地多变。因此，对该特定表位的识别主要由TCR的β链主导。我们得出结论，就反应性T细胞的多样性而言，B6小鼠对甲型流感病毒感染的小鼠CD8 +反应是有限的。然而，CD8 +反应具有显著的可塑性，能够轻易弥补主要T细胞群体的缺失。
