Role of T Cells in Chikungunya Virus Infection and Utilizing Their Potential in Anti-Viral Immunity

Abstract

Chikungunya virus (CHIKV) is an arthropod-borne alphavirus that causes hallmark debilitating polyarthralgia, fever, and rash in patients. T cell-mediated immunity, especially CD4⁺ T cells, are known to participate in the pathogenic role of CHIKV immunopathology. The other T cell subsets, notably CD8⁺, NKT, and gamma-delta (γδ) T cells, can also contribute to protective immunity, but their effect is not actuated during the natural course of infection. This review serves to consolidate and discuss the multifaceted roles of these T cell subsets during acute and chronic phases of CHIKV infection, and highlight gaps in the current literature. Importantly, the unique characteristics of skin-resident memory T cells are outlined to propose novel prophylactic strategies that utilize their properties to provide adequate, lasting protection.

Keywords: T cells; chikungunya; immunopathology; resident-memory T cells; vaccination.

Figure 1

The list of conserved CD8 epitopes in CHIKV that was identified in silico by others and published in the literature were arranged according to the positions they occupy along the CHIKV proteome. The immunogenicity scores are determined through the Immune Epitope Database (IEDB) and plotted as shown. Of all the CD8 epitopes, only the three epitopes in the 6K region are experimentally validated.

Figure 2

Summary of the roles each T cell subset play during acute CHIKV infection. (1) When CHIKV-infected mosquitoes transmit the virus to its human host (or experimental infection in mice), CHIKV infects the surrounding cells and creates pro-inflammatory milleu in the joints. (2) This serves to attract monocytes and NKT cells to the joints, which exacerbates the inflammation by secreting pro-inflammatory cytokines and chemokines, thereby potentiating the chemoattraction of other immune cells to the infection site. (3) The APCs that engulfs CHIKV antigens travel to lymphoid organs, present CHIKV epitopes to CD4 and CD8 T cells and activate them. Activated CD4 T cells then trigger CHIKV-specific B cells to develop antibodies that can neutralize the virus. Treg cells may also interact with APCs that ultimately lead to anergy in CHIKV-specific CD4 T cells. (4) Proliferating CD4 and CD8 T cells migrate to the swollen joints and contribute to the inflammation through IFN-γ secretion. Although not directly demonstrated, CHIKV-specific CD4 and CD8 T cells may recognize infected endothelial cells at the site of infection, leading to disruption of the barrier and worsens joint swelling.