Saltini C, Spurzem J R, Kirby M R, Crystal R G
Pulmonary Branch, National Heart, Lung, and Blood Institute, Bethesda, MD 20892.
J Immunol. 1988 Mar 15;140(6):1854-60.
In pulmonary sarcoidosis, the marked expansion of CD4+ (helper/inducer) T cells in the alveolar structures of the lung is maintained by local IL-2 release by activated CD4+ HLA-DR+ T cells without concomitant expansion and activation of CD8+ (suppressor/cytotoxic) T cells, suggesting that sarcoid may be associated with a generalized abnormality of CD8+ T cells. Consistent with this concept, evaluation of the expression of the IL-2R on fresh lung T cells from individuals with active sarcoidosis demonstrated that 7 +/- 1% of sarcoid lung CD4+ T cells are spontaneously expressing the IL-2R compared with only 1 +/- 1% lung CD8+ T cells (p less than 0.01). However, stimulation of purified sarcoid blood CD8+ T cells with the anti-T3/TCR complex mAb OKT3 was followed by the normal expression of IL-2R (p greater than 0.1) and proliferation (p greater than 0.1). In addition, lung sarcoid CD8+ T cells responded to OKT3 similarly to normal lung CD8+ T cells and to autologous blood CD8+ T cells as regards expression of IL-2R (p greater than 0.1) and proliferation (p greater than 0.1). Finally, using CD4+ cells activated with allogenic Ag to induce, in coculture, fresh autologous CD8+ cells to suppress proliferation of fresh autologous CD4+ cells to the same Ag, sarcoid CD8+ T cells suppressed CD4+ cell proliferation in a normal fashion (p greater than 0.1). These results demonstrate that sarcoid CD8+ (suppressor/cytotoxic) T cells are competent to respond to a proliferation signal normally and can be induced to normally suppress CD4+ T cell proliferation to Ag, suggesting that the expansion of activated CD4+ T cells in pulmonary sarcoidosis is not due to a generalized abnormality of CD8+ T cells or of their suppressor T cell function.
在肺结节病中,肺的肺泡结构中CD4 +(辅助/诱导)T细胞的显著扩增是由活化的CD4 + HLA - DR + T细胞局部释放IL - 2维持的,而CD8 +(抑制/细胞毒性)T细胞没有伴随扩增和活化,这表明结节病可能与CD8 + T细胞的全身性异常有关。与此概念一致的是,对活动性结节病患者新鲜肺T细胞上IL - 2R表达的评估表明,结节病肺CD4 + T细胞中有7±1%自发表达IL - 2R,而肺CD8 + T细胞中只有1±1%(p<0.01)。然而,用抗T3/TCR复合物单克隆抗体OKT3刺激纯化的结节病血液CD8 + T细胞后,IL - 2R正常表达(p>0.1)且细胞增殖(p>0.1)。此外,就IL - 2R表达(p>0.1)和增殖(p>0.1)而言,肺结节病CD8 + T细胞对OKT3的反应与正常肺CD8 + T细胞以及自体血液CD8 + T细胞相似。最后,用同种异体抗原激活的CD4 +细胞在共培养中诱导新鲜自体CD8 +细胞抑制新鲜自体CD4 +细胞对相同抗原的增殖,结节病CD8 + T细胞以正常方式抑制CD4 +细胞增殖(p>0.1)。这些结果表明,结节病CD8 +(抑制/细胞毒性)T细胞能够正常响应增殖信号,并且可以被诱导正常抑制CD4 + T细胞对抗原的增殖,这表明肺结节病中活化的CD4 + T细胞的扩增不是由于CD8 + T细胞或其抑制性T细胞功能的全身性异常。