Mycobacterium tuberculosis-specific CD4 T cells expressing transcription factors associate with bacterial control in granulomas

Abstract

ABSTRACTDespite the extensive research on CD4 T cells within the context ofMycobacterium tuberculosis(Mtb) infection, few studies have focused on identifying and investigating the profile of Mtb-specific T cells within lung granulomas. To facilitate identification of Mtb-specific CD4 T cells, we identified immunodominant epitopes for two Mtb proteins, Rv1196 and Rv0125, using a Mauritian cynomolgus macaque model of Mtb infection, providing data for the synthesis of MHC Class II tetramers. Using tetramers, we identified Mtb-specific cells within different immune compartments post-infection. We found that granulomas were enriched sites for Mtb-specific cells and that tetramer+cells had increased frequencies of the activation marker CD69, and transcription factors T-bet and RORγT, compared to tetramer negative cells within the same sample. Our data revealed that while the frequency of Rv1196 tetramer+cells was positively correlated with granuloma bacterial burden, the frequency of RORγT or T-bet within tetramer+cells was inversely correlated with granuloma bacterial burden highlighting the importance of having activated, functional Mtb-specific cells for control of Mtb in lung granulomas.