Distinct Immune Profiles of Exhausted Effector and Memory CD8+ T Cells in Individuals With Filarial Lymphedema

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dc.contributor.authorHorn, Sacha
dc.contributor.authorBorrero-Wolff, Dennis
dc.contributor.authorRitter, Manuel
dc.contributor.authorArndts, Kathrin
dc.contributor.authorWiszniewsky, Anna
dc.contributor.authorDebrah, Linda Batsa
dc.contributor.authorDebrah, Alexander Y.
dc.contributor.authorOsei-Mensah, Jubin
dc.contributor.authorChachage, Mkunde
dc.contributor.authorHoerauf, Achim
dc.contributor.authorKroidl, Inge
dc.contributor.authorLayland, Laura E.
dc.date.accessioned2022-11-23T15:56:06Z
dc.date.available2022-11-23T15:56:06Z
dc.date.issued2021-08-11
dc.description.abstractCD8+ 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+ T-cell subsets and exhaustion remains uncertain, especially during filariasis, a chronic helminth infection. Lymphatic filariasis, elicited by Wuchereria bancrofti, 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+ T cells were compared between asymptomatic Wuchereria bancrofti-infected individuals, uninfected endemic normals, and those with LE (grades 2–6). Focusing on exhausted memory (CD8+exmem: CD8+ T-betdimEomeshi) and effector (CD8+exeff: CD8+T-bethiEomesdim) CD8+ T-cell subsets, advanced flow cytometry revealed that LE individuals presented reduced frequencies of IFN-γ+CD8+exmem 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+CD8+exeff 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+ T-cell subsets are prominent in individuals suffering from LE, suggesting that enhanced inflammation and constant immune activation might drive exhaustion of CD8+ 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+ T-cell exhaustion patterns in filarial LE should be taken into consideration for prevention and control management of LE.en_US
dc.description.sponsorshipThis work was supported by the German Research Foundation (Deutsche Forschungsgemeinschaft – DFG) (RHINO project) [grants KR3615/1-1 and HO2009/11-1], German Federal Ministry of Education and Research (Bundesministerium für Bildung und Forschung - BMBF) [grant 01KA1601], and the German Center for Infection Research (Deutsches Zentrum für Infektionsforschung – DZIF) [grant TI03.907_00].en_US
dc.identifier.citationHorn Sacha, Borrero-Wolff Dennis, Ritter Manuel, Arndts Kathrin, Wiszniewsky Anna, Debrah Linda Batsa, Debrah Alexander Y., Osei-Mensah Jubin, Chachage Mkunde, Hoerauf Achim, Kroidl Inge, Layland Laura E (2021). Distinct Immune Profiles of Exhausted Effector and Memory CD8+ T Cells in Individuals With Filarial Lymphedema. Front. Cell. Infect. Microbiol. 11:680832. doi: 10.3389/fcimb.2021.680832en_US
dc.identifier.issn2235-2988
dc.identifier.urihttp://hdl.handle.net/20.500.11810/5908
dc.language.isoenen_US
dc.publisherFrontiers Media S.A.en_US
dc.subjectFilariae, CD8+ T cell exhaustion, Wuchereria bancrofti infection, lymphatic filariasis, immune modulation, lymphedema, memory and effector T cell subsetsen_US
dc.titleDistinct Immune Profiles of Exhausted Effector and Memory CD8+ T Cells in Individuals With Filarial Lymphedemaen_US
dc.title.alternativeCD8 Exhaustion Patterns in LFen_US
dc.typeJournal Article, Peer Revieweden_US
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