HIV-1 Infection Is Associated with Depletion and Functional Impairment of -Specific CD4 T Cells in Individuals with Latent Tuberculosis Infection.

Coinfection with HIV is the single greatest risk factor for reactivation of latent infection (LTBI) and progression to active tuberculosis disease. HIV-associated dysregulation of adaptive immunity by depletion of CD4 Th cells most likely contributes to loss of immune control of LTBI in HIV-infected individuals, although the precise mechanisms whereby HIV infection impedes successful T cell-mediated control of have not been well defined. To further delineate mechanisms whereby HIV impairs protective immunity to , we evaluated the frequency, phenotype, and functional capacity of -specific CD4 T cells in HIV-infected and HIV-uninfected adults with LTBI. HIV infection was associated with a lower total frequency of cytokine-producing -specific CD4 T cells, and preferential depletion of a discrete subset of -specific IFN-γIL-2TNF-α CD4 T cells. -specific CD4 T cells in HIV-infected individuals expressed significantly higher levels of Ki67, compared with HIV-uninfected individuals, thus indicating recent activation and turnover of these cells in vivo. The ex vivo proliferative capacity of -specific CD4 T cells was markedly impaired in HIV-infected individuals, compared with HIV-uninfected individuals. Moreover, HIV infection was associated with increased Ag-induced CD4 T cell death ex vivo, indicating a possible mechanism contributing to impaired proliferative capacity of -specific CD4 T cells in HIV-infected individuals. These data provide new insights into the parameters of -specific CD4 T cell immunity that are impaired in HIV-infected individuals with LTBI, which may contribute to their increased risk of developing active tuberculosis disease.