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

• Published in: Frontiers in cellular and infection microbiology Vol. 11; p. 680832
• Main Authors: Horn, 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.
• Format: Journal Article
• Language: English
• Published: Frontiers Media S.A 11.08.2021
• Subjects: CD8+ T cell exhaustion; Cellular and Infection Microbiology; Filariae; immune modulation; lymphatic filariasis; lymphedema; Wuchereria bancrofti infection
• ISSN: 2235-2988; 2235-2988
• DOI: 10.3389/fcimb.2021.680832

CD8 + 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 + ex mem : CD8 + T-bet dim Eomes hi ) and effector (CD8 + ex eff : CD8 + T-bet hi Eomes dim ) CD8 + T-cell subsets, advanced flow cytometry revealed that LE individuals presented reduced frequencies of IFN-γ + CD8 + ex mem 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 + ex eff 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.