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

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 , 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 -infected individuals, uninfected endemic normals, and those with LE (grades 2-6). Focusing on exhausted memory (CD8ex: CD8 T-betEomes) and effector (CD8ex: CD8T-betEomes) CD8 T-cell subsets, advanced flow cytometry revealed that LE individuals presented reduced frequencies of IFN-γCD8ex 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-10CD8ex 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.

Copyright © 2021 Horn, Borrero-Wolff, Ritter, Arndts, Wiszniewsky, Debrah, Debrah, Osei-Mensah, Chachage, Hoerauf, Kroidl and Layland.

PMID: 34485170