HIV-1 infection is associated with depletion and functional impairment of Mycobacterium tuberculosis-specific CD4 T cells in individuals with latent tuberculosis infection1

• Published in: The Journal of immunology (1950) 2017-07, Vol.199 (6), p.2069-2080
• Main Authors: Day, Cheryl L., Abrahams, Deborah A., Harris, Levelle D., van Rooyen, Michele, Stone, Lynnett, de Kock, Marwou, Hanekom, Willem A.
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1700558

Co-infection with HIV is the single greatest risk factor for reactivation of latent Mycobacterium tuberculosis infection (LTBI) and progression to active tuberculosis (TB) disease. HIV-associated dysregulation of adaptive immunity by depletion of CD4 T helper cells 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 Mtb have not been well defined. To further delineate mechanisms whereby HIV impairs protective immunity to M. tuberculosis (Mtb), we evaluated the frequency, phenotype, and functional capacity of Mtb-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 Mtb-specific CD4 T cells, and preferential depletion of a discrete subset of Mtb-specific IFN-γ + IL-2 − TNF-α + CD4 T cells. Mtb-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 Mtb-specific CD4 T cells was markedly impaired in HIV-infected individuals, compared with HIV-uninfected individuals. Moreover, HIV infection was associated with increased Mtb Ag-induced CD4 T cell death ex vivo, indicating a possible mechanism contributing to impaired proliferative capacity of Mtb-specific CD4 T cells in HIV-infected individuals. These data provide new insights into the parameters of Mtb-specific CD4 T cell immunity that are impaired in HIV-infected individuals with LTBI, which may contribute to their increased risk of developing active TB disease.