{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T20:10:44Z","timestamp":1790885444865,"version":"4.1.0"},"reference-count":150,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2024,8,30]],"date-time":"2024-08-30T00:00:00Z","timestamp":1724976000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Penelope and Ed Peskowitz","award":["129125"],"award-info":[{"award-number":["129125"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Since their conception with the smallpox vaccine, vaccines used worldwide have mitigated multiple pandemics, including the recent COVID-19 outbreak. Insightful studies have uncovered the complexities of different functional networks of CD4 T cells (T helper 1 (Th1); Th2, Th17) and CD8 T cells (T cytotoxic; Tc), as well as B cell (BIgM, BIgG, BIgA and BIgE) subsets, during the response to vaccination. Both T and B cell subsets form central, peripheral, and tissue-resident subsets during vaccination. It has also become apparent that each vaccination forms a network of T regulatory subsets, namely CD4+ CD25+ Foxp3+ T regulatory (Treg) cells and interleukin-10 (IL-10)-producing CD4+ Foxp3\u2212 T regulatory 1 (Tr1), as well as many others, which shape the quality\/quantity of vaccine-specific IgM, IgG, and IgA antibody production. These components are especially critical for immunocompromised patients, such as older individuals and allograft recipients, as their vaccination may be ineffective or less effective. This review focuses on considering how the pre- and post-vaccination Treg\/Tr1 levels influence the vaccination efficacy. Experimental and clinical work has revealed that Treg\/Tr1 involvement evokes different immune mechanisms in diminishing vaccine-induced cellular\/humoral responses. Alternative steps may be considered to improve the vaccination response, such as increasing the dose, changing the delivery route, and\/or repeated booster doses of vaccines. Vaccination may be combined with anti-CD25 (IL-2R\u03b1 chain) or anti-programmed cell death protein 1 (PD-1) monoclonal antibodies (mAb) to decrease the Tregs and boost the T\/B cell immune response. All of these data and strategies for immunizations are presented and discussed, aiming to improve the efficacy of vaccination in humans and especially in immunocompromised and older individuals, as well as organ transplant patients.<\/jats:p>","DOI":"10.3390\/vaccines12090992","type":"journal-article","created":{"date-parts":[[2024,8,30]],"date-time":"2024-08-30T09:39:32Z","timestamp":1725010772000},"page":"992","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["The Major Role of T Regulatory Cells in the Efficiency of Vaccination in General and Immunocompromised Populations: A Review"],"prefix":"10.3390","volume":"12","author":[{"given":"Stanislaw","family":"Stepkowski","sequence":"first","affiliation":[{"name":"Department of Medical Microbiology and Immunology, University of Toledo, Toledo, OH 43614, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3626-4310","authenticated-orcid":false,"given":"Dulat","family":"Bekbolsynov","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Immunology, University of Toledo, Toledo, OH 43614, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jared","family":"Oenick","sequence":"additional","affiliation":[{"name":"Neurological Surgery, The University of Toledo College of Medicine and Life Sciences, Toledo, OH 43614, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Surina","family":"Brar","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Immunology, University of Toledo, Toledo, OH 43614, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beata","family":"Mierzejewska","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Immunology, University of Toledo, Toledo, OH 43614, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A.","family":"Rees","sequence":"additional","affiliation":[{"name":"Department of Urology, The University of Toledo College of Medicine and Life Sciences, Toledo, OH 43614, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Obi","family":"Ekwenna","sequence":"additional","affiliation":[{"name":"Department of Urology, The University of Toledo College of Medicine and Life Sciences, Toledo, OH 43614, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,30]]},"reference":[{"key":"ref_1","first-page":"18","article-title":"Jenner and the control of smallpox","volume":"113","author":"Baxby","year":"1996","journal-title":"Trans. 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