AUTHOR=Horn Sacha , Ritter Manuel , Arndts Kathrin , Borrero-Wolff Dennis , Wiszniewsky Anna , Debrah Linda Batsa , Debrah Alexander Y. , Osei-Mensah Jubin , Chachage Mkunde , Hoerauf Achim , Kroidl Inge , Layland Laura E. 

TITLE=Filarial Lymphedema Patients Are Characterized by Exhausted CD4+ T Cells

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=Volume 11 - 2021

YEAR=2022

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2021.767306

DOI=10.3389/fcimb.2021.767306

ISSN=2235-2988

ABSTRACT=Worldwide, more than 200 million people are infected with filariae which can cause severe symptoms leading to reduced quality of life and contribute to disability-adjusted life years (DALYs). In particular, lymphatic filariasis (LF) caused by Wuchereria bancrofti can lead to lymphedema (LE) and consequently presents a serious health problem. To understand why only a fraction of the infected individuals develop pathology, it is essential to understand how filariae regulate host immunity. The central role of T cells for immunity against filariae has been shown in several studies. However, there is little knowledge known about T cell exhaustion, which causes cell dysfunction and impaired immune responses, in this group of individuals. Recently, we showed that LE patients from Ghana harbour distinct patterns of exhausted effector and memory CD8+ cell subsets. Based on these findings, we now characterized CD4+ cell subsets from the same Ghanaian patient cohort using a 13-colour flow cytometry panel. We revealed that LE patients had increased frequencies of CD4+ cells expressing exhaustion-associated receptors such as KLRG-1, TIM-3 and PD-1 compared to healthy endemic normal and W. bancrofti-infected individuals. Moreover, CD4+ cells in LE patients were characterized by distinct co-expression patterns of inhibitory receptors. Collectively with the previous findings on CD8+ T cell exhaustion patterns, the data shown here demonstrates that filarial LE patients harbour distinct subsets of exhausted T cells. Thus, T cell exhaustion patterns in LE patients need attention especially in regards to susceptibility of concomitant infections and should be taken into consideration for LE management measures.