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Cell. Infect. Microbiol."],"abstract":"<jats:p>CD8<jats:sup>+<\/jats:sup> T cells are crucial for the clearance of viral infections, and current research begins to highlight their importance in parasitic diseases too. In-depth research about characteristics of CD8<jats:sup>+<\/jats:sup> T-cell subsets and exhaustion remains uncertain, especially during filariasis, a chronic helminth infection. Lymphatic filariasis, elicited by <jats:italic>Wuchereria bancrofti<\/jats:italic>, remains a serious health problem in endemic areas in Ghana, especially in those suffering from morbidity due to lymphedema (LE). In this observational study, the characteristics and profiles of CD8<jats:sup>+<\/jats:sup> T cells were compared between asymptomatic <jats:italic>Wuchereria bancrofti<\/jats:italic>-infected individuals, uninfected endemic normals, and those with LE (grades 2\u20136). Focusing on exhausted memory (CD8<jats:sup>+<\/jats:sup>ex<jats:sub>mem<\/jats:sub>: CD8<jats:sup>+<\/jats:sup> T-bet<jats:sup>dim<\/jats:sup>Eomes<jats:sup>hi<\/jats:sup>) and effector (CD8<jats:sup>+<\/jats:sup>ex<jats:sub>eff<\/jats:sub>: CD8<jats:sup>+<\/jats:sup>T-bet<jats:sup>hi<\/jats:sup>Eomes<jats:sup>dim<\/jats:sup>) CD8<jats:sup>+<\/jats:sup> T-cell subsets, advanced flow cytometry revealed that LE individuals presented reduced frequencies of IFN-\u03b3<jats:sup>+<\/jats:sup>CD8<jats:sup>+<\/jats:sup>ex<jats:sub>mem<\/jats:sub> T cells expressing Tim-3 or LAG-3 which negatively correlated to the presence of LE. Moreover, the LE cohort further showed significantly higher frequencies of IL-10<jats:sup>+<\/jats:sup>CD8<jats:sup>+<\/jats:sup>ex<jats:sub>eff<\/jats:sub> T cells expressing either Tim-3, LAG-3, CD39, KLRG-1, or PD-1, all associated markers of exhaustion, and that these frequencies positively correlated with the presence of LE. In summary, this study shows that distinct exhausted CD8<jats:sup>+<\/jats:sup> T-cell subsets are prominent in individuals suffering from LE, suggesting that enhanced inflammation and constant immune activation might drive exhaustion of CD8<jats:sup>+<\/jats:sup> T cells. Since T-cell exhaustion is known to be associated with insufficient control of persisting antigen, the data presented here reveals that these CD8<jats:sup>+<\/jats:sup> T-cell exhaustion patterns in filarial LE should be taken into consideration for prevention and control management of LE.<\/jats:p>","DOI":"10.3389\/fcimb.2021.680832","type":"journal-article","created":{"date-parts":[[2021,8,11]],"date-time":"2021-08-11T06:20:00Z","timestamp":1628662800000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":17,"title":["Distinct Immune Profiles of Exhausted Effector and Memory CD8+ T Cells in Individuals With Filarial Lymphedema"],"prefix":"10.3389","volume":"11","author":[{"given":"Sacha","family":"Horn","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis","family":"Borrero-Wolff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Ritter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathrin","family":"Arndts","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Wiszniewsky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda Batsa","family":"Debrah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander Y.","family":"Debrah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jubin","family":"Osei-Mensah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mkunde","family":"Chachage","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Achim","family":"Hoerauf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inge","family":"Kroidl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura E.","family":"Layland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,8,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1179\/136485910X12786389891407","article-title":"Induction of Immunoglobulin G4 in Human Filariasis: An Indicator of Immunoregulation","volume":"104","author":"Adjobimey","year":"2010","journal-title":"Ann. 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