{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T23:41:04Z","timestamp":1787701264317,"version":"build-2784847793"},"reference-count":91,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T00:00:00Z","timestamp":1754870400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Anusandhan National Research foundation (ANRF), Science and Engineering Research Board (SERB), Department of Science and Technology (DST), Government of India","award":["CRG\/2021\/001362"],"award-info":[{"award-number":["CRG\/2021\/001362"]}]},{"name":"Anusandhan National Research foundation (ANRF), Science and Engineering Research Board (SERB), Department of Science and Technology (DST), Government of India","award":["45\/07\/2022-IMM\/BMS"],"award-info":[{"award-number":["45\/07\/2022-IMM\/BMS"]}]},{"name":"Indian Council of Medical Research (ICMR), Government of India, New Delhi","award":["CRG\/2021\/001362"],"award-info":[{"award-number":["CRG\/2021\/001362"]}]},{"name":"Indian Council of Medical Research (ICMR), Government of India, New Delhi","award":["45\/07\/2022-IMM\/BMS"],"award-info":[{"award-number":["45\/07\/2022-IMM\/BMS"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Introduction: Mycobacterium tuberculosis (Mtb), the most common co-infection among people living with HIV (PLWH), aggravates the associated morbidity and mortality in these individuals; however, the immune-modulatory role of Mtb in the pathogenesis of HIV infection remains incompletely understood. Methods: We investigated the role of Mtb infection in regulating adaptive immune responses with reference to the expression of five immune checkpoint molecules (ICMs) in co-infected individuals in a cross-sectional study conducted on treatment-na\u00efve human cohorts from North India, including PLWH, people with Mtb infection, people with HIV-Mtb co-infection, and healthy volunteers as controls. Results: The data revealed a significantly increased gene expression of TIM-3 (p = 0.0058), LAG-3 (p &lt; 0.0001), PD-1 (p = 0.0090), and CTLA-4 (p = 0.0008). It also revealed a higher frequency of CD4+ and CD8+ T-cells surface-expressing TIM-3+, CTLA-4+, LAG-3+. Finally, it showed cells co-expressing two ICMs together (p &lt; 0.05) in individuals with HIV\u2013Mtb co-infection as compared to HIV mono-infected ones. Interestingly, the frequency of these cells correlated inversely with the absolute CD4+ T-cell count and positively with the plasma viral load (p &lt; 0.05), indicating direct association with HIV disease progression. Conclusions: These findings suggest that Mtb co-infection exacerbates immune exhaustion in co-infected individuals. Targeting ICMs with pharmacological immune checkpoint inhibitors (ICIs) offers a promising approach for better clinical management of co-infected individuals.<\/jats:p>","DOI":"10.3390\/pathogens14080802","type":"journal-article","created":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T11:02:09Z","timestamp":1754910129000},"page":"802","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Mycobacterium tuberculosis Modulates the Expansion of Terminally Exhausted CD4+ and CD8+ T-Cells in Individuals with HIV-TB Co-Infection"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-2107-5629","authenticated-orcid":false,"given":"Komal","family":"Sharma","sequence":"first","affiliation":[{"name":"Molecular Immunology Laboratory, Department of Immunopathology, Post Graduate Institute of Medical Education & Research (PGIMER), Chandigarh 160012, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aman","family":"Sharma","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Post Graduate Institute of Medical Education & Research (PGIMER), Chandigarh 160012, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8294-5360","authenticated-orcid":false,"given":"Sunil K.","family":"Arora","sequence":"additional","affiliation":[{"name":"Molecular Immunology Laboratory, Department of Immunopathology, Post Graduate Institute of Medical Education & Research (PGIMER), Chandigarh 160012, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,11]]},"reference":[{"key":"ref_1","unstructured":"(2024, September 03). 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