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.

Automated summary

HIV/Mycobacterium tuberculosis (Mtb) co-infected individuals have an increased risk of tuberculosis before the loss of peripheral CD4 T cells. This study used rhesus macaques to investigate the early effects of simian immunodeficiency virus (SIV) co-infection on pulmonary granulomas. The results showed that Mtb-specific CD4 T cells were dramatically depleted from granulomas two weeks after SIV inoculation in Mtb-infected macaques, before CD4 T cell loss in blood, airways, and lymph nodes. The study also revealed reduced motility of intralesional CD4 T cells after SIV co-infection. These findings suggest that CD4 T cells in granulomas may be decimated before the onset of acute HIV infection symptoms.