Dengue virus infection elicits highly polarized CX3CR1+ cytotoxic CD4+ T cells associated with protective immunity

Infections with any of the four dengue virus serotypes (DENV 1-4) are the most prevalent and rapidly spreading mosquito-borne viral infections in humans. There is no treatment or vaccine currently available. We found that the virus-specific cells display a highly polarized cytotoxic phenotype that correlated with expression of a protective HLA DR allele. Although the occurrence of cytotoxic CD4⁺ T cells in humans has been described in the context of some chronic viral infections, to our knowledge, this is the first report of ex vivo cytotoxic CD4⁺ activity after exposure with an acute virus. These results will help shed light on the specific role of CD4⁺ T cells in DENV infection and may help in finding a correlate of protection.