Depletion of CD8+ T cells in vivo impairs host defense of mice resistant and susceptible to pulmonary paracoccidioidomycosis
Depletion of CD8+ T cells in vivo impairs host defense of mice resistant and susceptible to pulmonary paracoccidioidomycosis
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DOI：
10.1128/iai.68.1.352-359.2000
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发表时间：
2000-01-01
影响因子：
3.1
通讯作者：
Calich, VLG
中科院分区：
文献类型：
--
作者：
Cano, LE;Singer-Vermes, LM;Calich, VLG
使用肺部感染模型，我们先前证明了a /Sn和B10。A小鼠对巴西副球虫感染分别有抗性和易感。采用相同的实验模型，我们在此研究了CD8(+) T细胞在副球孢子菌病过程中的作用。抗cds单克隆抗体在两种小鼠品系中引起肺和脾CD8+ T细胞的选择性耗竭。肺CD4(+) T细胞和免疫球蛋白阳性细胞的数量与CD8(+) T细胞的数量无关。在易感小鼠中，体内抗cds单克隆抗体处理导致CD8(+) T细胞的丢失，损害了肺部对酵母菌的清除，增加了真菌向肝脏和脾脏的传播。在耐药小鼠中，同样的治疗增加了真菌向肺外组织的传播，但没有改变肺部真菌负荷。此外，CD8+ t细胞缺失并未改变A/Sn小鼠的延迟型超敏反应，但增加了B10的这些反应。一个老鼠。缺乏CD8+ T细胞的耐药和易感小鼠产生的巴西疟原虫特异性抗体与给予对照抗体的小鼠相似。组织病理学上，CD8(+) T细胞的耗竭并没有破坏两种小鼠品系发生的局灶性肉芽肿病变。这些结果表明，CD8(+) T细胞是清除巴西孢子虫感染小鼠组织中的真菌所必需的，并且在易感动物的免疫反应中显示出更突出的保护活性。
Using a pulmonary model of infection, we demonstrated previously that A/Sn and B10.A mice are, respectively, resistant and susceptible to Paracoccidioides brasiliensis infection. Employing the same experimental model, we examined herein the role of CD8(+) T cells in the course of paracoccidioidomycosis. Treatment with anti-CDS monoclonal antibodies caused a selective depletion of pulmonary and splenic CD8+ T cells in both mouse strains. The number of pulmonary CD4(+) T cells and immunoglobulin-positive cells was independent of the number of CD8(+) T cells. In susceptible mice, the loss of CD8(+) T cells by in vivo treatment with anti-CDS monoclonal antibodies impaired the clearance of yeasts from the lungs and increased the fungal dissemination to the liver and spleen. The same treatment in resistant mice increased fungal dissemination to extrapulmonary tissues but did not alter the pulmonary fungal load. Furthermore, CD8+ T-cell depletion did not modify delayed-type hypersensitivity reactions of A/Sn mice but increased these reactions in B10.A mice. The production of P. brasiliensis-specific antibodies by resistant and susceptible mice depleted of CD8+ T cells was similar to that of mice given control antibody. Histopathologically, depletion of CD8(+) T cells did not disorganize the focal granulomatous lesions developed by both mouse strains. These results indicate that CD8(+) T cells are necessary for optimal clearance of the fungus from tissues of mice infected with P. brasiliensis and demonstrate more prominent protective activity by those cells in the immune responses mounted by susceptible animals.