Filarial Lymphedema Patients Are Characterized by Exhausted CD4 + T Cells

• Published in: Frontiers in cellular and infection microbiology Vol. 11; p. 767306
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 06-01-2022
• Subjects: CD4+ T cell exhaustion; CD4-Positive T-Lymphocytes; Cellular and Infection Microbiology; Disability-Adjusted Life Years; filariae; Ghana; Humans; immune modulation; lymphatic filariasis; Lymphedema; Quality of Life; Wuchereria bancrofti infection; Ghana; lymphatic filariasis; CD4+ T cell exhaustion; Wuchereria bancrofti infection; immune modulation; lymphedema; filariae
• ISSN: 2235-2988; 2235-2988
• DOI: 10.3389/fcimb.2021.767306

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
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 about T cell exhaustion, which causes T cell dysfunction and impaired immune responses, in this group of individuals. Recently, we showed that LE patients from Ghana harbor distinct patterns of exhausted effector and memory CD8
T cell subsets. Based on these findings, we now characterized CD4
T cell subsets from the same Ghanaian patient cohort by analyzing distinct markers within a 13-colour flow cytometry panel. We revealed that LE patients had increased frequencies of CD4
T cells expressing exhaustion-associated receptors such as KLRG-1, TIM-3 and PD-1 compared to healthy endemic normal and
-infected individuals. Moreover, CD4
T 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 harbor 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.