Khetan S, Sainis K B, Rath S, Kamat R
Department of Immunology, Haffkine Institute, Parel, Bombay, India.
Eur J Immunol. 1993 Oct;23(10):2440-7. doi: 10.1002/eji.1830231010.
The mechanism of antigen-specific suppression and reasons for aberrant major histocompatibility complex (MHC) class II restriction mediated by CD8+ T cells was investigated in a previously reported murine model of immunosuppression, generated by intraperitoneal priming with Mycobacterium vaccae. Both the CD4+ T helper cells (Th) and CD8+ T suppressor cell (Ts) of M. vaccae-primed mice recognized the 65-kDa antigen of the bacillus, presented by I-A and I-E, respectively. The CD8+ Ts could inhibit non-antigen-specific proliferation of primed CD4+ T cells induced by the exogenously added interleukin (IL)-2 (concanavalin A-stimulated culture supernatant). For inhibition, the Ts had to be activated by the 65-kDa antigen. The degree of inhibition was dependent upon the amount of added IL-2 and the relative numbers of primed CD8+ and CD4+ T cells. On incubation with antigen-presenting cells, and the 65-kDa antigen, the primed CD8+ T cells absorbed IL-2 as efficiently as primed CD4+ T cells. Based on this, it was concluded that the primed CD8+ T cells induced suppression by competition for IL-2. Employing the same model, the MHC restriction of recognition of the suppressor epitope of the 65-kDa antigen by the CD8+ Ts was investigated. The epitopes presented by diverse MHC class II molecules, such as self I-A, I-E and even allogeneic I-E were similar, because they were recognized by the same population of primed CD8+ Ts. Further, immunization of C57BL/6 mice with Ltk-cells expressing H-2 DkKk alloantigens, stimulated CD8+ T cells capable of recognizing M.vaccae 65-kDa antigen. Based on these data, it was proposed that recognition of the suppressor epitope of the 65-kDa antigen by the primed CD8+ Ts exhibits lack of restriction specificity imposed by MHC diversity.
在先前报道的由腹腔注射母牛分枝杆菌引发免疫抑制的小鼠模型中，研究了抗原特异性抑制机制以及由CD8 + T细胞介导的异常主要组织相容性复合体（MHC）II类限制的原因。母牛分枝杆菌致敏小鼠的CD4 +辅助性T细胞（Th）和CD8 +抑制性T细胞（Ts）均识别该杆菌的65 kDa抗原，分别由I - A和I - E呈递。CD8 + Ts可抑制外源性添加白细胞介素（IL）-2（刀豆球蛋白A刺激的培养上清液）诱导的致敏CD4 + T细胞的非抗原特异性增殖。为实现抑制，Ts必须被65 kDa抗原激活。抑制程度取决于添加的IL - 2量以及致敏CD8 +和CD4 + T细胞的相对数量。与抗原呈递细胞和65 kDa抗原一起孵育时，致敏CD8 + T细胞吸收IL - 2的效率与致敏CD4 + T细胞相同。基于此，得出结论：致敏CD8 + T细胞通过竞争IL - 2诱导抑制作用。利用同一模型，研究了CD8 + Ts对65 kDa抗原抑制表位识别的MHC限制。由不同MHC II类分子呈递的表位，如自身I - A、I - E甚至同种异体I - E，是相似的，因为它们被同一群致敏CD8 + Ts识别。此外，用表达H - 2 DkKk同种异体抗原的Ltk -细胞免疫C57BL / 6小鼠，刺激了能够识别母牛分枝杆菌65 kDa抗原的CD8 + T细胞。基于这些数据，有人提出致敏CD8 + Ts对65 kDa抗原抑制表位的识别表现出缺乏由MHC多样性施加的限制特异性。
