Beck J M, Newbury R L, Palmer B E, Warnock M L, Byrd P K, Kaltreider H B
Department of Veterans Affairs Medical Center and the University of Michigan Medical Center, Ann Arbor, USA.
J Lab Clin Med. 1996 Nov;128(5):477-87. doi: 10.1016/s0022-2143(96)90044-x.
An improved understanding of host defense against Pneumocystis carinii could provide novel therapeutic modalities directed against this opportunistic pathogen. Immunodeficient mouse models confirm the role of CD4+ lymphocytes in defense against P. carinii, but the role of CD8+ lymphocytes is controversial. BALB/c mice specifically depleted of CD4+ lymphocytes are susceptible to P. carinii, recruiting large numbers of CD8+ lymphocytes to their lungs during infection. Because of this recruitment, we hypothesized that CD8+ lymphocytes could participate in host defense against P. carinii. BALB/c mice were depleted of CD4+ lymphocytes, CD8+ lymphocytes, or both CD4+ and CD8+ lymphocytes. All mice were then inoculated intratracheally with P. carinii. Mice depleted of CD4+ lymphocytes became moderately infected with P. carinii. Mice depleted of CD8+ lymphocytes cleared the inoculum, indicating that CD8+ lymphocytes are unnecessary for defense when CD4+ lymphocytes are available. However, mice depleted of both CD4+ and CD8+ lymphocytes became significantly more intensely infected than mice depleted of CD4+ lymphocytes alone. Therefore, CD8+ lymphocytes participate in defense against P. carinii in vivo during depletion of CD4+ lymphocytes. To determine the mechanisms of this protection, CD8+ lymphocytes were purified from the lungs of CD4-depleted mice during infection. Lung CD8+ lymphocytes proliferated in response to P. carinii antigen and elaborated interferon-gamma in vitro. Thus CD8+ lymphocytes provide defense against P. carinii in vivo, and the elaboration of interferon-gamma likely represents one important mechanism of defense. During states of CD4+ lymphocyte depletion, the modulation of CD8+ lymphocyte function may provide alternative approaches to the host defense against opportunistic pathogens.
对宿主抵御卡氏肺孢子虫的深入了解可为针对这种机会性病原体的新型治疗方法提供依据。免疫缺陷小鼠模型证实了CD4+淋巴细胞在抵御卡氏肺孢子虫中的作用，但CD8+淋巴细胞的作用存在争议。特异性清除CD4+淋巴细胞的BALB/c小鼠易感染卡氏肺孢子虫，感染期间肺部会募集大量CD8+淋巴细胞。由于这种募集现象，我们推测CD8+淋巴细胞可能参与宿主对卡氏肺孢子虫的防御。对BALB/c小鼠分别清除CD4+淋巴细胞、CD8+淋巴细胞或同时清除CD4+和CD8+淋巴细胞。然后所有小鼠经气管内接种卡氏肺孢子虫。清除CD4+淋巴细胞的小鼠受到中度感染。清除CD8+淋巴细胞的小鼠清除了接种物，这表明在有CD4+淋巴细胞时，CD8+淋巴细胞对防御并非必需。然而，同时清除CD4+和CD8+淋巴细胞的小鼠比仅清除CD4+淋巴细胞的小鼠感染明显更严重。因此，在CD4+淋巴细胞耗竭期间，CD8+淋巴细胞在体内参与对卡氏肺孢子虫的防御。为确定这种保护机制，在感染期间从清除CD4的小鼠肺部纯化CD8+淋巴细胞。肺CD8+淋巴细胞对卡氏肺孢子虫抗原产生增殖反应，并在体外产生γ干扰素。因此，CD8+淋巴细胞在体内提供对卡氏肺孢子虫的防御，γ干扰素的产生可能是一种重要的防御机制。在CD4+淋巴细胞耗竭状态下，调节CD8+淋巴细胞功能可能为宿主抵御机会性病原体提供替代方法。
