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.

γδ T cells modulate humoral immunity against Plasmodium berghei infection

“…5,9,19,23,26 The parasites were stored as frozen stock in liquid nitrogen or a deep freezer. 5,9,19,23,26 The parasites were stored as frozen stock in liquid nitrogen or a deep freezer.…”

“…3,4 This evidence strongly indicates that malaria-specific antibodies play a crucial role in protective immunity against malaria. 2,[9][10][11][12][13] IFN-c-signalling-deficient mice may exhibit decreased dendritic cell activation and T helper type 1 (Th1) responses during infection. 2,[9][10][11][12][13] IFN-c-signalling-deficient mice may exhibit decreased dendritic cell activation and T helper type 1 (Th1) responses during infection.…”

“…5,9,[14][15][16][17][18][19][20] As malaria cd T-cell numbers in peripheral blood and the spleen, cd T cells have been suggested to have a role in malaria. 5,9,[14][15][16][17][18][19][20] As malaria cd T-cell numbers in peripheral blood and the spleen, cd T cells have been suggested to have a role in malaria.…”

“…5,9,[14][15][16][17][18][19][20] As malaria cd T-cell numbers in peripheral blood and the spleen, cd T cells have been suggested to have a role in malaria. 9,22 Interferon-c activates phagocytosis by macrophages and monocytes. Inhibition of IFN-c signalling by gene knockout (KO) or injection of neutralizing anti-IFN-c antibody led to worsening of the parasitaemia, resulting in loss of fluctuation of the parasitaemia.…”

“…9,22 Interferon-c activates phagocytosis by macrophages and monocytes. 9 These observations lead to the question of whether cd T cells are involved in humoral immunity during PbXAT infection. In contrast to WT mice, cd T-cell-deficient T-cell receptor-d (TCR-d) KO mice cannot control PbXAT parasites, and they develop high parasitaemia and eventually die.…”