TB and HIV Drive Distinct and Separate Tissue Resident Memory Cell Subset Depletion

BackgroundTuberculosis (TB) and HIV co-infection cause profound immune dysregulation. Understanding how these infections alter immune cell distribution across systemic and tissue compartments is critical for improving therapeutic and vaccine strategies. MethodsFlow cytometry was used to quantify CD4 and CD8 T cells, B cells, and tissue-resident memory (TRM) T and B cells in peripheral blood mononuclear cells (PBMCs), lung tissue, bronchoalveolar lavage (BAL), spleen, and lung-draining hilar lymph nodes (HLN) from individuals with pulmonary TB (PTB), disseminated TB (Diss TB), HIV only, or both TB and HIV infections. ResultsCD4 T cell frequencies were significantly reduced in multiple compartments of HIV infected subjects, irrespective of TB status, indicating systemic immune suppression. CD8 T-cell frequencies were elevated in the blood of HIV-infected individuals, suggesting a compensatory response to CD4 T-cell loss. B-cell frequencies were reduced in PBMCs and lung tissue of TB subjects, regardless of HIV status. Notably, CD4 TRM T cells were specifically depleted in lung tissue of HIV/TB co-infected individuals, whereas TRM B cells were selectively depleted in TB subjects, independent of HIV infection. ConclusionTB and HIV drive distinct and compartment-specific TRM cell loss in infected tissues. HIV primarily targets CD4 TRM T cells, while TB specifically depletes TRM B cells, highlighting separate mechanisms of tissue-resident immune disruption. These findings emphasize the importance of tissue-specific immune analyses and provide new insights for targeted vaccine and immunotherapy strategies.