1. Phenotypic Profile of Mycobacterium tuberculosis-Specific CD4 T-Cell Responses in People With Advanced Human Immunodeficiency Virus Who Develop Tuberculosis-Associated Immune Reconstitution Inflammatory Syndrome.
- Author
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Moseki, Raymond M, Barber, Daniel L, Bruyn, Elsa Du, Shey, Muki, Plas, Helen Van der, Wilkinson, Robert J, Meintjes, Graeme, and Riou, Catherine
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IMMUNE reconstitution inflammatory syndrome ,HIV ,CD4 antigen ,T cells ,MYCOBACTERIUM ,MYCOBACTERIUM avium - Abstract
Background Tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) is a frequent complication of cotreatment for TB and human immunodeficiency virus (HIV)-1. We characterized Mycobacterium tuberculosis (Mtb)-specific CD4 T-cell phenotype and transcription factor profile associated with the development of TB-IRIS. Methods We examined the role of CD4 T-cell transcription factors in a murine model of mycobacterial IRIS. In humans, we used a longitudinal study design to compare the magnitude of antiretroviral therapy, activation, transcription factor profile, and cytotoxic potential of Mtb-specific CD4 T cells between TB-IRIS (n = 25) and appropriate non-IRIS control patients (n = 18) using flow cytometry. Results In the murine model, CD4 T-cell expression of Eomesodermin (Eomes), but not Tbet, was associated with experimentally induced IRIS. In patients, TB-IRIS onset was associated with the expansion of Mtb-specific IFNγ
+ CD4 T cells (P =.039). Patients with TB-IRIS had higher HLA-DR expression (P =.016), but no differences in the expression of T-bet or Eomes were observed. At TB-IRIS onset, Eomes+ Tbet+ Mtb-specific IFNγ+ CD4+ T cells showed higher expression of granzyme B in patients with TB-IRIS (P =.026). Conclusions Although the murine model of Mycobacterium avium complex-IRIS suggests that Eomes+ CD4 T cells underly IRIS, TB-IRIS was not associated with Eomes expression in patients. Mycobacterium tuberculosis -specific IFNγ+ CD4 T-cell responses in TB-IRIS patients are differentiated, highly activated, and potentially cytotoxic. [ABSTRACT FROM AUTHOR]- Published
- 2023
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