Chikungunya virus-specific CD4+ T cells are associated with chronic chikungunya viral arthritic disease in humans
Rimjhim Agarwal, James Chang, Fernanda Heloise Côrtes, Calvin Ha, John Villalpando, Izabella N. Castillo, Rosa Isela Gálvez, Alba Grifoni, Alessandro Sette, Claudia M. Romero-Vivas, Mark T. Heise, Lakshmanane Premkumar, Andrew K. Falconar, Daniela Weiskopf
Abstract
Chikungunya virus (CHIKV) is a mosquito-borne virus that can cause chronic chikungunya virus disease (CHIKVD), which is characterized by persistent incapacitating arthralgia. Despite recurring CHIKV outbreaks and recent approval of a vaccine, the breadth and target of T cell responses in CHIKVD remain largely understudied. Here, we tested peripheral blood mononuclear cells (PBMCs) collected from CHIKV-infected individuals against overlapping peptide pools sequentially spanning the entire CHIKV proteome. We detected robust CHIKV-specific CD4 + , but not CD8 + , T cell responses in infected individuals. Individuals with chronic arthralgia displayed significantly higher CD4 + T cell responses against nsP1, nsP2, and E2 proteins and exhibited a significantly lower Th1 CD4 + T cell population, compared to individuals who had recovered. Additionally, CD4 + T cells in chronic individuals were marked by a predominant production of tumor necrosis factor alpha (TNF-α). Overall, our work comprehensively characterizes T cell responses in CHIKVD in humans and provides insights into the role of T cells in CHIKVD.