biostudies-literatureAgarwal RNIAID NIH HHS102134https://www.ebi.ac.uk/biostudies/studies/S-EPMC12147901biostudies-literatureUnknown6(5)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 TCell reports. MedicineChikungunya virus-specific CD4<sup>+</sup> T cells are associated with chronic chikungunya viral arthritic disease in humans.PMC1214790175N93019C00065U24 AI152170Sette AAgarwal RFalconar AKPremkumar LCortes FHGalvez RIGrifoni AHeise MTWeiskopf DCastillo INRomero-Vivas CMVillalpando JChang JHa CfalseChikungunya virus-specific CD4<sup>+</sup> T cells are associated with chronic chikungunya viral arthritic disease in humans.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 T2025-01-01T00:00:00Z2025 May2026-04-25T03:22:08.702Z2026-04-25T03:20:34.494ZS-EPMC121479014039839210.1016/j.xcrm.2025.102134