Curtis J L, Byrd P K, Warnock M L, Beck J M, Kaltreider H B
Pulmonary and Critical Care Medicine Section, VA Medical Center, San Francisco, California 94121.
Am J Respir Cell Mol Biol. 1993 Jul;9(1):90-8. doi: 10.1165/ajrcmb/9.1.90.
CD8+ T cells predominate in the lungs in hypersensitivity and human immunodeficiency virus-related lymphocytic pneumonitis, but their role in the immunopathogenesis of lung disease is unknown. We have shown that in immunized mice depleted of CD4+ T cells, CD8+ T cells are recruited into the lungs in response to intratracheal antigen challenge with sheep red blood cells (SRBC) (J. Clin. Invest. 1991; 88:1244-1254) or to pulmonary infection with Pneumocystis carinii (Am. J. Respir. Cell Mol. Biol. 1991; 5:186-197), suggesting that recruitment of CD8+ T cells does not depend on CD4+ T cell-derived signals. Because CD8+ T cells themselves produce a variety of chemotactic and immunoregulatory cytokines, CD8+ T cells may be important participants in, and modulators of, pulmonary immune responses. To test this hypothesis, we examined the effects of CD8+ T cell depletion on the generation of a pulmonary immune response in vivo. We monitored the recruitment of mononuclear cells into lungs in the absence of CD8-dependent signals and measured the duration of pulmonary inflammation in the absence of suppressor CD8+ T cells. Primed mice were treated with anti-CD8 monoclonal antibody to deplete CD8+ T cells and subsequently were challenged intratracheally with 5 x 10(8) SRBC. At various times after challenge, total and differential cell counts and lymphocyte phenotypes were measured in bronchoalveolar lavage fluid by flow cytometry and lungs were scored histologically. We found that depletion of CD8+ T cells neither decreased recruitment of immune and inflammatory cells nor prolonged the pulmonary immune response.(ABSTRACT TRUNCATED AT 250 WORDS)
在超敏反应以及与人类免疫缺陷病毒相关的淋巴细胞性肺炎中,CD8 + T细胞在肺部占主导地位,但其在肺部疾病免疫发病机制中的作用尚不清楚。我们已经表明,在CD4 + T细胞耗竭的免疫小鼠中,CD8 + T细胞会因气管内注射绵羊红细胞(SRBC)抗原攻击(《临床研究杂志》1991年;88:1244 - 1254)或卡氏肺孢子虫肺部感染(《美国呼吸与细胞分子生物学杂志》1991年;5:186 - 197)而被募集到肺部,这表明CD8 + T细胞的募集不依赖于CD4 + T细胞衍生的信号。由于CD8 + T细胞自身会产生多种趋化性和免疫调节细胞因子,CD8 + T细胞可能是肺部免疫反应的重要参与者和调节者。为了验证这一假设,我们研究了CD8 + T细胞耗竭对体内肺部免疫反应产生的影响。我们监测了在缺乏CD8依赖性信号的情况下单核细胞向肺部的募集情况,并测量了在缺乏抑制性CD8 + T细胞的情况下肺部炎症的持续时间。用抗CD8单克隆抗体处理致敏小鼠以耗竭CD8 + T细胞,随后气管内注射5×10(8)个SRBC进行攻击。在攻击后的不同时间,通过流式细胞术测量支气管肺泡灌洗液中的总细胞计数和分类细胞计数以及淋巴细胞表型,并对肺部进行组织学评分。我们发现,CD8 + T细胞的耗竭既没有减少免疫细胞和炎性细胞的募集,也没有延长肺部免疫反应。(摘要截选至250字)