Up-regulation of VCAM-1 and differential expansion of β integrin-expressing T lymphocytes are associated with immunity to pulmonary Mycobacterium tuberculosis infection
Up-regulation of VCAM-1 and differential expansion of β integrin-expressing T lymphocytes are associated with immunity to pulmonary Mycobacterium tuberculosis infection
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DOI：
10.4049/jimmunol.164.9.4853
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发表时间：
2000-05-01
影响因子：
4.4
通讯作者：
Bean, AGD
中科院分区：
文献类型：
--
作者：
Feng, CG;Britton, WJ;Bean, AGD
免疫应答依赖于一个复杂的粘附分子系统，以协调次级淋巴组织和感染部位淋巴细胞的归巢和滞留。为了确定与肺免疫应答相关的事件，分析了结核分枝杆菌感染期间T细胞上内皮地址素和整合素的表达。在感染的肺，表达的内皮细胞VCAM-1，但不是粘膜地址素细胞粘附分子-1，上调从4周感染后，并持续到至少12周。随后对肺CD 4（+）和CD 8（+）T细胞上表达的相应整联蛋白的分析揭示了在感染期间β（1）（高）/β（7）（-/低）和在较小程度上β（7）（高）整联蛋白表达T细胞的积累。整联蛋白异源二聚体的检查显示，虽然α（4）整联蛋白主要在β（1）（高）/β（7）（-/低）细胞上表达，但α（E）整联蛋白主要与β（7）（高）相关。在感染期间募集的大多数活化/记忆T细胞表达高水平的β（1）整联蛋白和不可检测或低水平的β（7）整联蛋白。这些T细胞能够产生IFN-γ，一种对控制M至关重要的细胞因子。肺结核感染。在继发性分枝杆菌感染后，肺中β（1）（高）、β（7）（-）和β（7）（高）T细胞群的快速扩增表明这些群体参与了对感染的获得性免疫应答。此外，用α（4）或α（4）β（7）整联蛋白的mAb治疗感染小鼠，导致肺浸润中淋巴细胞减少和粒细胞增加。这些结果揭示了粘附分子在产生有效的肺免疫应答中的关键作用。肺结核感染。
Immune responses rely on an intricate system of adhesion molecules to coordinate the homing and retention of lymphocytes in both secondary lymphoid tissues and at sites of infection. To define the events associated with pulmonary immune responses, the expression of endothelial addressins and integrins on T cells was analyzed during Mycobacterium tuberculosis infection. In infected lung, expression of endothelial VCAM-1, but not mucosal addressin cell adhesion molecule-1, was up-regulated from 4 wk postinfection and persisted to at least 12 wk. Subsequent analysis of the corresponding integrins expressed on lung CD4(+) and CD8(+) T cells revealed an accumulation of beta(1)(high)/beta(7)(-/low), and to a lesser extent beta(7)(high), integrin expressing T cells during infection. Examination of integrin heterodimers showed that while alpha(4) integrin was predominantly expressed on beta(1)(high)/beta(7)(-/low) cells, alpha(E) integrin was primarily associated with beta(7)(high). The majority of activated/memory T cells recruited during infection expressed high levels of beta(1) integrin and undetectable or low levels of beta(7) integrin. These T cells were capable of producing IFN-gamma, a cytokine crucial for controlling M. tuberculosis infection. Rapid expansion of beta(1)(high), beta(7)(-), and beta(7)(high) T cell populations in the lung upon secondary mycobacterial infection indicates the participation of these populations in the acquired immune response to the infection. Furthermore, treatment of infected mice with mAb to alpha(4) or alpha(4)beta(7) integrin led to a reduction in lymphocytes and increase in granulocytes in the pulmonary infiltrate. These results reveal a crucial role for adhesion molecules in the generation of an effective pulmonary immune response to M. tuberculosis infection.