The Antigen-Presenting Potential of Vγ39Vδ 2 T Cells during Plasmodium falciparum Blood-Stage Infection

Abstract

During Plasmodium falciparum infections, erythrocyte-stage parasites inhibit dendritic cell maturation and function, compromising effective antimalarial adaptive immunity. Human V39V2 T cells can act in vitro as antigen-presenting cells (APCs) and induce αβ T-cell activation. However, the relevance of this activity in vivo has remained elusive. Because V39V2 T cells are activated during the early immune response against P. falciparum infection, we investigated whether they could contribute to the instruction of adaptive immune responses toward malaria parasites. In P. falciparum-infected patients, V39V2 T cells presented increased surface expression of APC-associated markers HLA-DR and CD86. In response to infected red blood cells in vitro, V39V2 T cells upregulated surface expression of HLA-DR, HLA-ABC, CD40, CD80, CD83, and CD86, induced naive αβ T-cell responses, and cross- presented soluble prototypical protein to antigen-specific CD8 + T cells. Our findings qualify V39Vcells as alternative APCs, which could be harnessed for therapeutic interventions and vaccine design.