Human filarial infection reshapes CD8⁺ T-cell transcription and function at homeostasis and following viral activation

The role of CD8⁺ T cells in filarial infections remains poorly understood. Given the chronic nature of these infections, individuals living in endemic regions are frequently exposed to other pathogens including viruses. Because CD8 cells are essential for antiviral immunity, understanding how filarial infections shape the cytotoxic compartment is essential to elucidate their impact on bystander immunity. We evaluated the phenotype and function of CD8⁺ T cells from Loa loa-infected (Fil⁺) and -uninfected (Fil^–) individuals at baseline and following cytomegalovirus (CMV) re-stimulation. Filarial infection was associated with increased activation and proliferation of CD8⁺ T cells, characterized by elevated expression of Ki-67, CD107a, and production of type 1 and 17 cytokines. Upon CMV re-stimulation, Fil⁺ individuals showed markedly reduced expansion of antigen-experienced (CD137⁺) and polyfunctional (CD137⁺IFN-γ⁺TNF-α⁺, CD137⁺IFN-γ⁺TNF-α⁺IL-2⁺) CD8⁺ T cells, along with decreased cytotoxic activity. Unbiased clustering analysis revealed markedly reduced frequency of the CD8⁺CD45RA⁺CD57⁺ subset in Fil⁺ individuals- a population further defined through transcriptomic profiling that showed enrichment for cytolytic gene signatures (GZMB, GNLY, GZMH, CD244, CX3CR1). These results demonstrated that filarial infection is associated with an altered CD8⁺ T cell profile that is associated with failure to mount effective viral-specific effector responses, including impaired cytokine production and cytotoxic activity.

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