{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T23:15:58Z","timestamp":1785798958174,"version":"3.56.0"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,10,26]],"date-time":"2021-10-26T00:00:00Z","timestamp":1635206400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:p>Antigen-specific gamma-delta (\u03b3\u03b4) T cells are important in exhibiting anti-mycobacterial immunity, but their role in latent tuberculosis (LTB) with diabetes mellitus (DM) or pre-DM (PDM) and non-DM comorbidities have not been studied. Thus, we have studied the baseline, mycobacterial (PPD, WCL), and positive control antigen-stimulated \u03b3\u03b4 T cells expressing Th1 (IFN\u03b3, TNF\u03b1, IL-2) and Th17 (IL-17A, IL-17F, IL-22) cytokine as well as cytotoxic (perforin [PFN], granzyme [GZE B], granulysin [GNLSN]) and immune (GMCSF, PD-1, CD69) markers in LTB (DM, PDM, NDM) comorbidities by flow cytometry. In the unstimulated (UNS) condition, we did not observe any significant difference in the frequencies of \u03b3\u03b4 T cells expressing Th1 and Th17 cytokine, cytotoxic, and immune markers. In contrast, upon PPD antigen stimulation, the frequencies of \u03b3\u03b4 T cells expressing Th1 (IFN\u03b3, TNF\u03b1) and Th17 (IL-17F, IL-22) cytokine, cytotoxic (PFN, GZE B, GNLSN), and immune (CD69) markers were significantly diminished in LTB DM and\/or PDM individuals compared to LTB NDM individuals. Similarly, upon WCL antigen stimulation, the frequencies of \u03b3\u03b4 T cells expressing Th1 (TNF\u03b1) and Th17 (IL-17A, IL-22) cytokine, cytotoxic (PFN), and immune (PD-1, CD69) markers were significantly diminished in LTB DM and\/or PDM individuals compared to LTB NDM individuals. Finally, upon P\/I stimulation we did not observe any significant difference in the \u03b3\u03b4 T cell frequencies expressing cytokine, cytotoxic, and immune markers between the study populations. The culture supernatant levels of IFN\u03b3, TNF\u03b1, and IL-17A cytokines were significantly increased in LTB DM and PDM after stimulation with Mtb antigens compared to LTB NDM individuals. Therefore, diminished \u03b3\u03b4 T cells expressing cytokine, cytotoxic, and other immune markers and elevated levels of cytokines in the supernatants is a characteristic feature of LTB PDM\/DM co-morbidities.<\/jats:p>","DOI":"10.3389\/fcimb.2021.756854","type":"journal-article","created":{"date-parts":[[2021,10,26]],"date-time":"2021-10-26T06:06:17Z","timestamp":1635228377000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":22,"title":["Decreased Frequencies of Gamma\/Delta T Cells Expressing Th1\/Th17 Cytokine, Cytotoxic, and Immune Markers in Latent Tuberculosis-Diabetes\/Pre-Diabetes Comorbidity"],"prefix":"10.3389","volume":"11","author":[{"given":"Gokul Raj","family":"Kathamuthu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathella Pavan","family":"Kumar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kadar","family":"Moideen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pradeep A.","family":"Menon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Subash","family":"Babu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,10,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1007\/s11892-009-0032-7","article-title":"Pathophysiology of Prediabetes","volume":"9","author":"Abdul-Ghani","year":"2009","journal-title":"Curr. 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