Reconstitution of CD4 T Cells in Bronchoalveolar Lavage Fluid after Initiation of Highly Active Antiretroviral Therapy

Abstract

The massive depletion of gastrointestinal-tract CD4 T cells is a hallmark of the acute phase of HIV infection.In contrast, the depletion of the lower-respiratory-tract mucosal CD4 T cells as measured in bronchoalveolar lavage (BAL) fluid is more moderate and similar to the depletion of CD4 T cells observed in peripheral blood (PB). To understand better the dynamics of disease pathogenesis and the potential for the reconstitution of CD4 T cells in the lung and PB following the administration of effective antiretroviral therapy, we studied cell-associated viral loads, CD4 T-cell frequencies, and phenotypic and functional profiles of antigen-specific CD4 T cells from BAL fluid and blood before and after the initiation of highly active antiretroviral therapy (HAART). The major findings to emerge were the following: (i) BAL CD4 T cells are not massively depleted or preferentially infected by HIV compared to levels for PB; (ii) BAL CD4 T cells reconstitute after the initiation of HAART, and their infection frequencies decrease; (iii) BAL CD4 T-cell reconstitution appears to occur via the local proliferation of resident BAL CD4 T cells rather than redistribution; and (iv) BAL CD4T cells are more polyfunctional than CD4 T cells in blood, and their functional profile is relatively unchanged after the initiation of HAART. Taken together, these data suggest mechanisms for mucosal CD4 T-cell depletion and interventions that might aid in the reconstitution of mucosal CD4 T cells.

Interaction between HIV and Mycobacterium tuberculosis: HIV-1-induced CD4 T-cell depletion and the development of active tuberculosis

“…Blocking viral replication by HAART initiation reverses CD4 T cell depletion within tissueair interphase [49] and reduces the risk-to develop active TB by at least 70% [29]. Together these data demonstrate that the site of primary MTB infection is particularly vulnerable to AIDS virus induced immune defects.…”

“…Substantial and progressive depletion of CD4 T cell within tissue-air interphase is also characteristic for chronic HIV infection humans [47][48][49]. Human tissue-air interphase CD4 T cells are EM T cells as characterized by a CD45RA-/CCR7-/CD27-phenotype [47][48].…”

Immunodeficiency lentiviral infections in natural and non-natural hosts

“…Specifically, the ability of Th1 type T cells to simultaneously produce multiple effector cytokines, such as IL-2, TNF-␣, and IFN-␥, is decreased among CD4 T cells from progressively HIV/SIV-infected subjects compared with uninfected subjects. [28][29][30] These functional abnormalities are not solely attributed to direct viral infection as functional abnormalities are also observed among CD8 T cells (which are only rarely infected by the virus in vivo). 20,28 Hence, loss of functionality among both CD4 and CD8 memory T cells may, in part, underlie the immunodeficiency associated with progressive HIV/SIV infections.…”

HIV-Associated Lung Infections and Complications in the Era of Combination Antiretroviral Therapy

“…After starting ART, the total number and percentage of BAL lymphocytes decreases due exclusively to a decrease in CD8 1 T lymphocytes in the alveolar space (14). CD4 1 cells in the BAL fluid reconstitute with ART, and their infection rate decreases (18).…”