Lung T cells in HIV infection. Driven to exhaustion?
Lung T cells in HIV infection. Driven to exhaustion?
复制标题
HIV 感染中的肺 T 细胞。
DOI：
10.1164/rccm.201501-0011ed
复制
发表时间：
2015
影响因子：
24.7
通讯作者：
Medoff,BenjaminD
中科院分区：
文献类型：
--
作者：
Cho,JosalynL;Medoff,BenjaminD
More than 30 million people are living with HIV worldwide, the majority of whom will suffer at least one pulmonary complication during the course of their disease (1, 2). Pulmonary infections remain an important cause of morbidity and mortality. Recent studies have also identified chronic, noninfectious pulmonary disorders, such as chronic obstructive pulmonary disease (COPD), as an emerging problem in HIV-positive individuals, even in those receiving effective antiretroviral therapy (ART)(3, 4). The fundamental pathogenic process in HIV infection is the depletion of CD4+ T cells, resulting in immunodeficiency and susceptibility to infection. The loss of CD4+ T cells is thought to result predominantly from chronic immune activation (5, 6). In fact, the level of immune activation predicts outcomes independent of viral load and CD4+ T cell counts. Chronic stimulation of T cells also drives the cells to exhaustion, an immune state characterized by increased expression of inhibitory markers and defined by the loss of effector functions (proliferative capacity, cytokine production, and cytotoxicity)(7).Even with effective viral suppression, immune activation persists at mucosal sites and predicts non-AIDS-related morbidity and mortality (6, 8). Activation of the immune system in the gut and female genital tract is associated with organ-specific immunologic defects and structural alterations that predispose HIV-positive individuals to both infectious and noninfectious disorders (9, 10). In the lung, chronic immune activation from HIV infection results in lymphocytic alveolitis (11, 12). Prior studies have documented depletion of CD4+ T cells and accumulation of CD8+ T cells in bronchoalveolar lavage (BAL) fluid. Lymphocytic alveolitis has been associated with increased mortality and has been implicated in the development of noninfectious pulmonary diseases (4, 13). Although there is a general understanding that HIV infection drives immune activation in the lung, a number of important questions remain: What are the mechanisms that drive lymphocytic alveolitis? What are the pathologic implications of this chronic inflammation in the lung? How are these processes altered by ART, environmental exposures, and microbes?
