TY - JOUR AU - Bucşan, Allison N. AU - Chatterjee, Ayan AU - Singh, Dhiraj K. AU - Foreman, Taylor W. AU - Lee, Tae-Hyung AU - Threeton, Breanna AU - Kirkpatrick, Melanie G. AU - Ahmed, Mushtaq AU - Golden, Nadia AU - Alvarez, Xavier AU - Hoxie, James A. AU - Mehra, Smriti AU - Rengarajan, Jyothi AU - Khader, Shabaana A. AU - Kaushal, Deepak T1 - Mechanisms of reactivation of latent tuberculosis infection due to SIV coinfection PY - 2019/12/02/ AB - HIV is a major driver of tuberculosis (TB) reactivation. Depletion of CD4+ T cells is assumed to be the basis behind TB reactivation in individuals with latent tuberculosis infection (LTBI) coinfected with HIV. Nonhuman primates (NHPs) coinfected with a mutant simian immunodeficiency virus (SIVΔGY) that does not cause depletion of tissue CD4+ T cells during infection failed to reactivate TB. To investigate the contribution of CD4+ T cell depletion relative to other mechanisms of SIV-induced reactivation of LTBI, we used CD4R1 antibody to deplete CD4+ T cells in animals with LTBI without lentiviral infection. The mere depletion of CD4+ T cells during LTBI was insufficient in generating reactivation of LTBI. Instead, direct cytopathic effects of SIV resulting in chronic immune activation, along with the altered effector T cell phenotypes and dysregulated T cell homeostasis, were likely mediators of reactivation of LTBI. These results revealed important implications for TB control in HIV-coinfected individuals. JF - The Journal of Clinical Investigation JA - J Clin Invest SN - 0021-9738 DO - 10.1172/JCI125810 VL - 129 IS - 12 UR - https://doi.org/10.1172/JCI125810 SP - 5254 EP - 5260 PB - The American Society for Clinical Investigation ER -