Preferentially expanding V[gamma]1+ [gamma][delta] T cells are associated with protective immunity against Plasmodium infection in mice

• Published in: European journal of immunology 2017-04, Vol.47 (4), p.685
• Main Authors: Inoue, Shin-Ichi, Niikura, Mamoru, Asahi, Hiroko, Iwakura, Yoichiro, Kawakami, Yasushi, Kobayashi, Fumie
• Format: Article
• Language: English
• Subjects: Infections; Lymphocytes; T cell receptors
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/eji.201646699

[gamma][delta] T cells play a crucial role in controlling malaria parasites. Dendritic cell (DC) activation via CD40 ligand (CD40L)-CD40 signaling by [gamma][delta] T cells induces protective immunity against the blood-stage Plasmodium berghei XAT (PbXAT) parasites in mice. However, it is unknown which [gamma][delta] T-cell subset has an effector role and is required to control the Plasmodium infection. Here, using antibodies to deplete TCR V[gamma]1+ cells, we saw that V[gamma]1+ [gamma][delta] T cells were important for the control of PbXAT infection. Splenic V[gamma]1+ [gamma][delta] T cells preferentially expand and express CD40L, and both V[gamma]1+ and V[gamma]4+ [gamma][delta] T cells produce IFN-[gamma] during infection. Although expression of CD40L on V[gamma]1+ [gamma][delta] T cells is maintained during infection, the IFN-[gamma] positivity of V[gamma]1+ [gamma][delta] T cells is reduced in late-phase infection due to [gamma][delta] T-cell dysfunction. In Plasmodium-infected IFN-[gamma] signaling-deficient mice, DC activation is reduced, resulting in the suppression of [gamma][delta] T-cell dysfunction and the dampening of [gamma][delta] T-cell expansion in the late phase of infection. Our data suggest that V[gamma]1+ [gamma][delta] T cells represent a major subset responding to PbXAT infection and that the V[gamma]1+ [gamma][delta] T-cell response is dependent on IFN-[gamma]-activated DCs.