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CD4 T regulatory cells (CD4 Tregs) have been investigated in common variable immunodeficiency (CVID). Recently, additional members have been added to the club of regulatory lymphocytes. These include CD8 T regulatory (CD8 Tregs), B regulatory (Bregs), and T follicular helper regulatory (T<jats:sub>FR<\/jats:sub>) cells. There are accumulating data to suggest their roles in both human and experimental models of autoimmune disease. Their phenotypic characterization and mechanisms of immunoregulation are evolving. Patients with CVID may present or are associated with an increased frequency of autoimmunity and autoimmune diseases. In this review, we have primarily focused on the characteristics of CD4 Tregs and new players of the regulatory club and their changes in patients with CVID in relation to autoimmunity and emphasized the complexity of interplay among various regulatory lymphocytes. We suggest future careful investigations of phenotypic and functional regulatory lymphocytes in a large cohort of phenotypic and genotypically defined CVID patients to define their role in the pathogenesis of CVID and autoimmunity associated with CVID.<\/jats:p>","DOI":"10.3389\/fimmu.2022.864307","type":"journal-article","created":{"date-parts":[[2022,5,20]],"date-time":"2022-05-20T10:33:56Z","timestamp":1653042836000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":13,"title":["Members of the Regulatory Lymphocyte Club in Common Variable Immunodeficiency"],"prefix":"10.3389","volume":"13","author":[{"given":"Sudhir","family":"Gupta","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yesim","family":"Demirdag","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ankmalika 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