{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T20:06:41Z","timestamp":1792613201042,"version":"4.5.0"},"reference-count":51,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2020,3,24]],"date-time":"2020-03-24T00:00:00Z","timestamp":1585008000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2020,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Prolonged therapy, drug toxicity, noncompliance, immune suppression, and alarming emergence of drug resistance necessitate the search for therapeutic vaccine strategies for tuberculosis (TB). Such strategies ought to elicit not only IFN\u2010\u03b3, but polyfunctional response including TNF\u2010\u03b1, which is essential for protective granuloma formation. Here, we investigated the impact of PD\u20101 inhibition in facilitating protective polyfunctional T\u00a0cells (PFTs), bacillary clearance, and disease resolution. We have observed PD\u20101 inhibition preferentially rescued the suppressed PFTs in active tuberculosis patients. In addition, polyfunctional cytokine milieu favored apoptosis of infected MDMs over necrosis with markedly reduced bacillary growth (\u226aCFU) in our in vitro monocyte\u2010derived macrophages (MDMs) infection model. Furthermore, the animal study revealed a significant decline in the bacterial burden in the lungs and spleen of infected mice after in vivo administration of \u03b1\u2010PD\u20101 along with antitubercular treatment. Our findings suggest that rescuing polyfunctional immune response by PD\u20101 inhibition works synergistically with antituberculosis chemotherapy to confer improved control over bacillary growth and dissemination. In summary, our data strongly indicate the therapeutic potential of \u03b1\u2010PD\u20101 as adjunct immunotherapy that can rejuvenate suppressed host immunity and enhance the efficacy of candidate therapeutic vaccine(s).<\/jats:p>","DOI":"10.1002\/eji.201948283","type":"journal-article","created":{"date-parts":[[2020,2,29]],"date-time":"2020-02-29T18:24:25Z","timestamp":1583000665000},"page":"736-747","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Improved Mycobacterium tuberculosis clearance after the restoration of IFN\u2010\u03b3\n                    <sup>+<\/sup>\n                    TNF\u2010\u03b1\n                    <sup>+<\/sup>\n                    CD4\n                    <sup>+<\/sup>\n                    T cells: Impact of PD\u20101 inhibition in active tuberculosis patients"],"prefix":"10.1002","volume":"50","author":[{"given":"Divya","family":"Kamboj","sequence":"first","affiliation":[{"name":"Department of Transplant Immunology &amp; Immunogenetics All India Institute of Medical Sciences  New Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pushpa","family":"Gupta","sequence":"additional","affiliation":[{"name":"Animal Experimentation Laboratory National JALMA Institute for Leprosy and other Mycobacterial Diseases  Agra India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mandira Varma","family":"Basil","sequence":"additional","affiliation":[{"name":"Department of Microbiology Vallabhbhai Patel Chest Institute University of Delhi  Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anant","family":"Mohan","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine &amp; Sleep Disorders All India Institute of Medical Sciences  New Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Randeep","family":"Guleria","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine &amp; Sleep Disorders All India Institute of Medical Sciences  New Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anuj","family":"Bhatnagar","sequence":"additional","affiliation":[{"name":"Department of Chest &amp; 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