The Antigen-Presenting Potential of Vγ9Vδ2 T Cells During Plasmodium falciparum Blood-Stage Infection

During Plasmodium falciparum infections, erythrocyte-stage parasites inhibit dendritic cell maturation and function, compromising effective antimalarial adaptive immunity. Human V gamma 9V delta 2 T cells can act in vitro as antigen-presenting cells (APCs) and induce alpha beta T-cell activation. However, the relevance of this activity in vivo has remained elusive. Because V gamma 9V delta 2 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, V gamma 9V delta 2 T cells presented increased surface expression of APC-associated markers HLA-DR and CD86. In response to infected red blood cells in vitro, V gamma 9V delta 2 T cells upregulated surface expression of HLA-DR, HLA-ABC, CD40, CD80, CD83, and CD86, induced naive alpha beta T-cell responses, and cross-presented soluble prototypical protein to antigen-specific CD8(+) T cells. Our findings qualify V gamma 9V delta 2 T cells as alternative APCs, which could be harnessed for therapeutic interventions and vaccine design.