Preferentially expanding Vγ1+ γδ T cells are associated with protective immunity against Plasmodium infection in mice

Abstract

γδ T cells play a crucial role in controlling malaria parasites. Dendritic cell (DC) activation via CD40 ligand (CD40L)-CD40 signaling by γδ T cells induces protective immunity against the blood-stage Plasmodium berghei XAT (PbXAT) parasites in mice. However, it is unknown which γδ T-cell subset has an effector role and is required to control the Plasmodium infection. Here, using antibodies to deplete TCR Vγ1⁺ cells, we saw that Vγ1⁺ γδ T cells were important for the control of PbXAT infection. Splenic Vγ1⁺ γδ T cells preferentially expand and express CD40L, and both Vγ1⁺ and Vγ4⁺ γδ T cells produce IFN-γ during infection. Although expression of CD40L on Vγ1⁺ γδ T cells is maintained during infection, the IFN-γ positivity of Vγ1⁺ γδ T cells is reduced in late-phase infection due to γδ T-cell dysfunction. In Plasmodium-infected IFN-γ signaling-deficient mice, DC activation is reduced, resulting in the suppression of γδ T-cell dysfunction and the dampening of γδ T-cell expansion in the late phase of infection. Our data suggest that Vγ1⁺ γδ T cells represent a major subset responding to PbXAT infection and that the Vγ1⁺ γδ T-cell response is dependent on IFN-γ-activated DCs.

Keywords: CD40L; Dendritic cells; IFN-γ; Malaria; Vγ1+ γδ T cells; γδ T cells; γδ T-cell exhaustion.