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

Abstract

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^dimEomes^hi) and effector (CD8⁺ex_eff: CD8⁺T-bet^hiEomes^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.

Keywords: CD8+ T cell exhaustion; Filariae; Wuchereria bancrofti infection; immune modulation; lymphatic filariasis; lymphedema; memory and effector T cell subsets.