CD4 T cells are rapidly depleted from tuberculosis granulomas following acute SIV co-infection.

HIV /Mycobacterium tuberculosis (Mtb) co-infected individuals have an increased risk of tuberculosis prior to loss of peripheral CD4 T cells, raising the possibility that HIV co-infection leads to CD4 T cell depletion in lung tissue before it is evident in blood. Here, we use rhesus macaques to study the early effects of simian immunodeficiency virus (SIV) co-infection on pulmonary granulomas. Two weeks after SIV inoculation of Mtb-infected macaques, Mtb-specific CD4 T cells are dramatically depleted from granulomas, before CD4 T cell loss in blood, airways, and lymph nodes, or increases in bacterial loads or radiographic evidence of disease. Spatially, CD4 T cells are preferentially depleted from the granuloma core and cuff relative to B cell-rich regions. Moreover, live imaging of granuloma explants show that intralesional CD4 T cell motility is reduced after SIV co-infection. Thus, granuloma CD4 T cells may be decimated before many co-infected individuals experience the first symptoms of acute HIV infection. [Display omitted] • SIV rapidly replicates in Mtb granulomas of co-infected macaques • Granuloma CD4 T cells are depleted before those in blood, BAL, LNs, or spleen • CCR5⁺Eomes⁻ Mtb-specific Th1 and Th1^∗ cells in granulomas are preferentially depleted • SIV co-infection reduces motility of CD4 T cells in granulomas HIV-mediated destruction of CD4 T cells enhances susceptibility to Mycobacterium tuberculosis. Using macaques, Foreman et al. show that CD4 T cells in granulomas are depleted very rapidly after SIV co-infection, indicating that loss of immunity at the site of bacterial replication occurs long before signs of peripheral T cell depletion. [ABSTRACT FROM AUTHOR]