THE ROLE OF CD4(+) AND CD8(+) T-CELLS IN THE PROTECTIVE INFLAMMATORY RESPONSE TO A PULMONARY CRYPTOCOCCAL INFECTION
THE ROLE OF CD4(+) AND CD8(+) T-CELLS IN THE PROTECTIVE INFLAMMATORY RESPONSE TO A PULMONARY CRYPTOCOCCAL INFECTION
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DOI：
10.1002/jlb.55.1.35
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发表时间：
1994-01-01
影响因子：
5.5
通讯作者：
STREET, NE
中科院分区：
文献类型：
--
作者：
HUFFNAGLE, GB;LIPSCOMB, MF;STREET, NE
中等毒力菌株的新型隐球菌，通过气管接种，引起肺部感染的BALB/c小鼠，逐渐解决的T淋巴细胞依赖性机制。目前使用单克隆抗体耗竭T细胞亚群的研究表明，CD 4（+）和CD 8（+）T细胞联合介导了显著的肺部炎症浸润，包括淋巴细胞、巨噬细胞、中性粒细胞和嗜酸性粒细胞。炎症反应在感染后2周达到峰值，并与感染的逐渐肺清除开始一致。CD_4/CD_8双缺陷（4（-）8（-））显著减少所有细胞流入肺。与CD 8缺乏相比，CD 4缺乏对肺部炎症细胞总数的影响更深远。CD 8（+）或CD 4（+）T细胞的耗竭显著减少肺巨噬细胞和中性粒细胞，但只有CD 4缺乏阻止嗜酸性粒细胞的流入。CD 8（+）T细胞的募集独立于CD 4（+）T细胞发生，但在CD 8缺陷小鼠中，CD 4（+）T细胞向肺部的募集显著减少。来自感染4（+）8（+）小鼠的丝裂原刺激的浸润性肺淋巴细胞分泌1型T辅助细胞（Th 1）[干扰素-γ（IFN-γ）和白细胞介素-2（IL-2）]和Th 2（IL-4、IL-5和IL-10）细胞因子。CD 4缺乏导致分泌IL-4、IL-5和IL-10的T细胞的损失。然而，残余的CD 8（+）T细胞仍然分泌IL-2和IFN-γ。与4（+）8（+）小鼠相比，来自CD 8缺陷小鼠的肺T细胞在每个肺的基础上分泌相似水平的IL-4、IL-5和IL-10，尽管CD 4（+）T细胞的数量减少，但分泌减少水平的IFN-γ。这些实验表明：（1）CD 4（+）T细胞在向肺募集巨噬细胞和粒细胞中起主导作用，（2）CD 8（+）T细胞也介导细胞募集，增加浸润中CD 4（+）T细胞数量的幅度，并有助于局部分泌IPN-γ。因此，这些研究表明，CD 8（+）T细胞可以独立地介导对大颗粒细胞外抗原的炎症反应，迄今为止，这一作用几乎完全归因于CD 4（+）T细胞。
Moderately virulent strains of Cryptococcus neoformans, inoculated via the trachea, cause a pulmonary infection in BALB/c mice that was gradually resolved by T lymphocyte-dependent mechanisms. The current studies, using monoclonal antibodies to deplete T cell subsets, demonstrated that CD4(+) and CD8(+) T cells combined to mediate a prominent pulmonary inflammatory infiltrate that included lymphocytes, macrophages, neutrophils, and eosinophils. The inflammatory response peaked 2 weeks after infection and coincided with the beginning of gradual pulmonary clearance of the infection. CD4/CD8 double deficiency (4(-)8(-)) markedly reduced the influx of all cells into the lungs. A CD4 deficiency had a more profound effect on the total number of inflammatory cells recruited to the lungs than a CD8 deficiency. Depletion of either CD8(+) or CD4(+) T cells significantly decreased pulmonary macrophages and neutrophils, but only a CD4 deficiency prevented the influx of eosinophils. Recruitment of CD8(+) T cells occurred independently of CD4(+) T cells, but CD4(+) T cell recruitment to the lungs was significantly reduced in CD8-deficient mice. Mitogen-stimulated infiltrating lung lymphocytes from infected 4(+)8(+) mice secreted both T helper cell type 1 (Th1) [interferon-gamma (IFN-gamma) and interleukin-2 (IL-2)] and Th2 (IL-4, IL-5, and IL-10) cytokines. CD4 deficiency resulted in loss of T cells secreting IL-4, IL-5, and IL-10. However, residual CD8(+) T cells still secreted IL-2 and IFN-gamma. Lung T cells from CD8-deficient mice secreted similar levels of IL-4, IL-5, and IL-10 on a per lung basis compared with 4(+)8(+) mice despite decreased numbers of CD4(+) T cells, but secreted reduced levels of lFN-gamma. These experiments indicate that (1) CD4(+) T cells play a dominant role in recruiting macrophages and granulocytes to the lung and (2) CD8(+) T cells also mediate cellular recruitment, increase the magnitude of CD4(+) T cell numbers in the infiltrate, and contribute to the local secretion ofIPN-gamma. Thus, these studies demonstrate that CD8(+) T cells can independently mediate an inflammatory response to a large, particulate, extracellular antigen, a role heretofore attributed almost solely to CD4(+) T cells.