Croix Denise A, Board Kathryn, Capuano Saverio, Murphey-Corb Michael, Haidaris Constantine G, Flynn Joanne L, Reinhart Todd, Norris Karen A
Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA.
AIDS Res Hum Retroviruses. 2002 Mar 20;18(5):391-401. doi: 10.1089/088922202753519179.
The goal of this study was to examine SIV- and Pneumocystis carinii-coinfected rhesus macaques as a model of P. carinii infection in HIV-seropositive humans. The influence of P. carinii infection on the cellular composition of bronchoalveolar lavage (BAL) fluid from SIV-infected and normal rhesus macaques was examined by flow cytometric analysis and polymerase chain reaction (PCR). BAL fluid from SIV- and P. carinii coinfected macaques showed a substantial T lymphocyte influx composed of more than 90% CD8+ T cells. These results are in contrast to BAL fluid from SIV-infected macaques with no detectable P. carinii-specific PCR product, where CD4+ T cells were present in significant numbers and the CD8+ T cell population was less than 70% of total CD3+ lymphocytes. We observed no significant differences in peripheral blood CD4+ or CD8+ T cell levels in the SIV-infected animals, regardless of P. carinii status, indicating that the CD8+ T cell infiltration in the lungs of the P. carinii-positive animals was likely the result of P. carinii infection. These results demonstrate that although peripheral blood CD4+ T cell levels are predictive of susceptibility to P. carinii infection in this model, the levels are not reflective of the T cell profile in the lung during SIV and P. carinii coinfection. The SIV- and P. carinii-coinfected macaques showed a spectrum of lung disease severity that was histologically similar to human P. carinii pneumonia (PCP). Interestingly, even mild P. carinii infection was sufficient to alter the normal CD4+/CD8+ T cell profiles in the lungs of SIV-infected rhesus macaques. These results are similar to immunologic findings in human AIDS-associated PCP and support the usefulness of this model in the study of immune responses to P. carinii.
本研究的目的是将感染猴免疫缺陷病毒（SIV）和卡氏肺孢子虫的恒河猴作为HIV血清阳性人类卡氏肺孢子虫感染的模型进行研究。通过流式细胞术分析和聚合酶链反应（PCR）检测卡氏肺孢子虫感染对SIV感染的恒河猴和正常恒河猴支气管肺泡灌洗（BAL）液细胞组成的影响。SIV和卡氏肺孢子虫共感染猕猴的BAL液显示大量T淋巴细胞流入，其中超过90%为CD8+T细胞。这些结果与未检测到卡氏肺孢子虫特异性PCR产物的SIV感染猕猴的BAL液形成对比，后者存在大量CD4+T细胞，且CD8+T细胞群体占总CD3+淋巴细胞的比例小于70%。我们观察到，无论卡氏肺孢子虫感染状态如何，SIV感染动物外周血CD4+或CD8+T细胞水平均无显著差异，这表明卡氏肺孢子虫阳性动物肺部的CD8+T细胞浸润可能是卡氏肺孢子虫感染的结果。这些结果表明，尽管外周血CD4+T细胞水平可预测该模型中对卡氏肺孢子虫感染的易感性，但该水平并不能反映SIV和卡氏肺孢子虫共感染期间肺部的T细胞谱。SIV和卡氏肺孢子虫共感染的猕猴表现出一系列肺部疾病严重程度，其组织学特征与人类卡氏肺孢子虫肺炎（PCP）相似。有趣的是，即使是轻度的卡氏肺孢子虫感染也足以改变SIV感染的恒河猴肺部正常的CD4+/CD8+T细胞谱。这些结果与人类艾滋病相关PCP的免疫学发现相似，并支持该模型在研究对卡氏肺孢子虫免疫反应中的有用性。
