CD8 T cells modulate CD4 T-cell and eosinophil-mediated pulmonary pathology in Pneumocystis pneumonia in B-cell-deficient mice
CD8 T cells modulate CD4 T-cell and eosinophil-mediated pulmonary pathology in Pneumocystis pneumonia in B-cell-deficient mice
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DOI：
10.2353/ajpath.2006.050724
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发表时间：
2006-02-01
影响因子：
6
通讯作者：
Harmsen, AG
中科院分区：
文献类型：
--
作者：
Swain, SD;Meissner, NN;Harmsen, AG
肺孢子虫属人类和替代动物物种中的肺炎（PCP）通常在缺乏CD 4 T细胞的情况下发生，如在获得性免疫缺陷综合征期间发生的那样。然而，接受高活性抗逆转录病毒治疗的患者有时会出现疾病恶化，如PCP，与CD 4 T细胞的复苏相一致，这种现象称为免疫重建疾病。我们使用了PCP的动物模型，使用B细胞缺陷的μ MT小鼠连同抗体介导的各种T细胞亚群的耗竭，以检查CD 4和CD 8 T细胞在PCP病理学发展中的作用。尽管明显的病理学发生在仅CD 4 T细胞、仅CD 8 T细胞或两者的存在下，但肺损伤通过不同的途径发生，这取决于存在的T细胞的补体。令人惊讶的是，当仅存在CD 4 T细胞时发生了严重的损伤，并且这种病理学与肺泡环境中嗜酸性粒细胞的增强的募集和活化以及强烈的2型细胞因子极化相一致。此外，CD 8 T细胞可以起到缓和这种CD 4 T细胞介导的病理学的作用，可能是通过增加推定的CD 25（+）抑制性CD 4 T细胞与CD 25（-）效应性CD 4 T细胞的比率。
Pneumocystis spp. pneumonia (PCP) in humans and in surrogate animal species typically occurs in the absence of CD4 T cells, as takes place during acquired immune deficiency syndrome. However, patients treated with highly active anti-retroviral therapy sometimes exhibit an exacerbation of diseases such as PCP that coincides with resurgent CD4 T cells, a phenomenon known as immune reconstitution disease. We used an animal model of PCP using the B-cell-deficient mu MT mouse together with antibody-mediated depletion of various T-cell subsets to examine the role of CD4 and CD8 T cells in the development of pathology in PCP. Although overt pathology occurs in the presence of CD4 T cells only, CD8 T cells only, or both, pulmonary injury occurs via different paths, depending on the complement of T cells present. Surprisingly, profound damage occurred when only CD4 T cells were present, and this pathology coincided with enhanced recruitment and activation of eosinophils and strong type 2 cytokine polarization in the alveolar environment. In addition, CD8 T cells can act to moderate this CD4 T cell-mediated pathology, possibly by increasing the ratio of putative CD25(+) suppressor CD4 T cells to CD25(-) effector CD4 T cells.