Uyemura K, Pirmez C, Sieling P A, Kiene K, Paes-Oliveira M, Modlin R L
Division of Dermatology, UCLA School of Medicine 90024.
J Immunol. 1993 Dec 15;151(12):7095-104.
The mechanism of protective immunity and immunologic resistance against intracellular pathogens is believed to involve the activation of Ag-specific T cells. The T cells involved in protection/resistance to Leishmania can be studied using localized American cutaneous leishmaniasis (LCL) as a model, because the disease is often self-healing. Our study was undertaken to identify specific T cell populations that had accumulated in LCL lesions on the basis of TCR V beta gene usage. RNA was derived from skin lesions and blood of eight LCL patients, as well as from purified CD4+ and CD8+ subsets from the lesions and blood of three patients. After synthesis of cDNA, V beta gene usage was assessed by polymerase chain reaction. In all eight patients, several V beta gene families were overrepresented in lesions compared to blood. More importantly, the TCR V beta repertoires of both lesional CD4+ and CD8+ subsets were skewed compared to the repertoire of the respective subsets in the blood of the same donor. The overrepresented V beta s in the CD4+ and CD8+ subsets from lesions were in most instances disparate, particularly with the V beta 6 TCR skewed in the lesional CD8+ subset. Not only were the TCR repertoires of the overrepresented V beta in the lesional CD4+ and CD8+ subsets generally distinct, but the cytokine mRNA expressed by these subsets were also discrete. Strikingly, the CD4+ subset was characterized by IFN-gamma mRNA expression and the CD8+ subset by IL-4 and IL-10 mRNA expression. These data indicate that the pathogenesis of human leishmaniasis may be explained by the balance of CD4+ type 1 and CD8+ type 2 T cells, which probably recognize distinct sets of Ag.
保护性免疫和针对细胞内病原体的免疫抗性机制被认为涉及抗原特异性T细胞的激活。由于局部性美洲皮肤利什曼病（LCL）通常可自愈，因此可以将其作为模型来研究参与对利什曼原虫保护/抗性的T细胞。我们的研究旨在根据TCR Vβ基因使用情况，鉴定在LCL病变中积累的特定T细胞群体。RNA取自8例LCL患者的皮肤病变组织和血液，以及3例患者病变组织和血液中纯化的CD4 +和CD8 +亚群。合成cDNA后，通过聚合酶链反应评估Vβ基因的使用情况。在所有8例患者中，与血液相比，病变组织中有几个Vβ基因家族的表达明显过高。更重要的是，与同一供体血液中相应亚群的TCR Vβ库相比，病变组织中CD4 +和CD8 +亚群的TCR Vβ库存在偏差。病变组织中CD4 +和CD8 +亚群中表达过高的Vβ在大多数情况下是不同的，特别是病变组织中的CD8 +亚群中Vβ6 TCR存在偏差。不仅病变组织中CD4 +和CD8 +亚群中表达过高的Vβ的TCR库通常不同，而且这些亚群表达的细胞因子mRNA也不同。引人注目的是，CD4 +亚群的特征是IFN-γ mRNA表达，而CD8 +亚群的特征是IL-4和IL-10 mRNA表达。这些数据表明，人类利什曼病的发病机制可能可以用CD4 + 1型和CD8 + 2型T细胞的平衡来解释，这两种T细胞可能识别不同的抗原组。
