Huffnagle G B, Yates J L, Lipscomb M F
Department of Pathology, University of Texas Southwestern Medical Center, Dallas 75235.
J Exp Med. 1991 Apr 1;173(4):793-800. doi: 10.1084/jem.173.4.793.
The role of CD4+ and CD8+ T cells in mediating pulmonary clearance of a cryptococcal infection was investigated. Intratracheal inoculation of BALB/c and C.B-17 mice with a moderately virulent strain of Cryptococcus neoformans (52D) resulted in a pulmonary infection, which was cleared by a T cell-dependent mechanism. During this clearance, there was a significant influx of both CD4+ and CD8+ T cells into the lungs. Depletion of CD4+ T cells by injections of CD4-specific monoclonal antibody (mAb) prevented pulmonary clearance and also resulted in significant colonization of the brain and spleen of infected mice. CD4 depletion did not prevent the influx of CD8+ T cells into the lungs. Surprisingly, depletion of CD8+ T cells by mAb also ablated pulmonary clearance. CD8-depleted mice also had a small but significant increase in brain and spleen colony-forming unit compared to control mice by the end of the study. CD4+ T cell pulmonary influx was independent of the presence of CD8+ T cells. The lungs of T cell-depleted mice were examined histologically. CD4+ and CD8+ T cells each mediated a degree of inflammatory influx seen in the lungs of infected mice and raised the possibility that CD4+ and CD8+ T cells may synergize to generate the inflammatory response in the lungs. Numerous phagocytized but intact cryptococci were seen in the inflammatory foci of CD8-depleted mice but not in control or CD4-depleted mice. We propose that CD4+ T cells may recruit and activate effector phagocytes while CD8+ T cells predominantly function to lyse cryptococcus-laden unactivated phagocytes similar to the function of CD8+ T cells during listeria and mycobacteria infections.
研究了CD4+和CD8+ T细胞在介导肺清除新型隐球菌感染中的作用。用中等毒力的新型隐球菌菌株（52D）气管内接种BALB/c和C.B-17小鼠，导致肺部感染，该感染通过T细胞依赖性机制清除。在清除过程中，CD4+和CD8+ T细胞大量涌入肺部。注射CD4特异性单克隆抗体（mAb）耗尽CD4+ T细胞可阻止肺部清除，并导致感染小鼠的脑和脾脏大量定植。CD4耗尽并未阻止CD8+ T细胞涌入肺部。令人惊讶的是，用mAb耗尽CD8+ T细胞也消除了肺部清除。到研究结束时，与对照小鼠相比，CD8耗尽的小鼠脑和脾脏集落形成单位也有小幅但显著的增加。CD4+ T细胞向肺部的涌入与CD8+ T细胞的存在无关。对T细胞耗尽小鼠的肺部进行了组织学检查。CD4+和CD8+ T细胞各自介导了感染小鼠肺部出现的一定程度的炎症细胞涌入，并增加了CD4+和CD8+ T细胞可能协同产生肺部炎症反应的可能性。在CD8耗尽小鼠的炎症灶中可见大量吞噬但完整的隐球菌，而在对照或CD4耗尽小鼠中未见。我们提出CD4+ T细胞可能招募并激活效应吞噬细胞，而CD8+ T细胞的主要功能是裂解载有隐球菌且未激活的吞噬细胞，这类似于CD8+ T细胞在李斯特菌和分枝杆菌感染期间的功能。
