{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T22:58:14Z","timestamp":1791845894720,"version":"4.3.4"},"reference-count":180,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T00:00:00Z","timestamp":1785715200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Tuberculosis (TB) and chronic obstructive pulmonary disease (COPD) remain global public health challenges, yet the mechanisms underlying their comorbidity remain poorly understood. COPD is associated with an increased risk of active TB, but the cellular and molecular basis of this association remains unclear. A growing body of evidence suggests that TB is not limited to an intramacrophage infection but is accompanied by a disruption of the local immune balance in lung tissue. This review analyzes the early interface of host\u2013Mycobacterium tuberculosis (Mtb) interaction\u2014from pattern recognition signaling pathways and metabolic reprogramming of macrophages to epithelial barrier responses and the delayed \u03b1\u03b2 T cell response. This review evaluates \u03b3\u03b4 T cells, particularly phosphoantigen (pAg)-reactive V\u03b39V\u03b42 cells, as a candidate early integrative component of the host response, positioned between macrophage infection, epithelial stress, mycobacterial antigens, and bacille Calmette\u2013Gu\u00e9rin (BCG)-induced trained immunity. Available evidence suggests that COPD-associated immune alterations may impair mucociliary clearance, antimicrobial peptide production, phagocytosis, and innate T cell responses while favoring cytotoxic reactions, the IL-17A\u2013G-CSF\u2013neutrophil axis, and protease-mediated tissue damage; however, direct mechanistic evidence in patients with TB\u2013COPD remains limited. It is important to note the differences in data obtained from studies in humans, primates, mice, and in vitro: the V\u03b39V\u03b42 system has no direct analog in laboratory mice, which represents a key limitation for preclinical studies. A key unresolved question remains the nature and functional consequences of \u03b3\u03b4 T cell changes in patients with coexisting COPD and TB infection. The answer to this question could inform new strategies for the prevention and treatment of TB in patients with COPD, including BCG revaccination, pAg-mediated immunomodulation, and the development of biomarkers to distinguish between protective and harmful early immune responses.<\/jats:p>","DOI":"10.3390\/ijms27156965","type":"journal-article","created":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T12:57:56Z","timestamp":1785761876000},"page":"6965","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["\u03b3\u03b4 T Cells at the Crossroads of Tuberculosis and COPD: From Early Immunity to Tissue Remodeling"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8966-2702","authenticated-orcid":false,"given":"Dmitry","family":"Oskin","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases and Phthisiology, Ryazan State Medical University, 390026 Ryazan, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7083-2692","authenticated-orcid":false,"given":"Stanislav","family":"Kotlyarov","sequence":"additional","affiliation":[{"name":"Department of Nursing, Ryazan State Medical University, 390026 Ryazan, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,3]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2025). 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