Enhancement of dendritic cell activation via CD40 ligand-expressing γδ T cells is responsible for protective immunity to Plasmodium parasites.

Abstract:

:Previous reports have shown that γδ T cells are important for the elimination of malaria parasites in humans and mice. However, how γδ T cells are involved in protective immunity against blood-stage malaria remains unknown. We infected γδ T-cell-deficient (TCRδ-KO) mice and control wild-type mice with Plasmodium berghei XAT, which is a nonlethal strain. Although infected red blood cells were eliminated within 30 d after infection, TCRδ-KO mice could not clear the infected red blood cells, showed high parasitemia, and eventually died. Therefore, γδ T cells are essential for clearance of the parasites. Here, we found that γδ T cells play a key role in dendritic cell activation after Plasmodium infection. On day 5 postinfection, γδ T cells produced IFN-γ and expressed CD40 ligand during dendritic cell activation. These results suggest that γδ T cells enhance dendritic cell activation via IFN-γ and CD40 ligand-CD40 signaling. This hypothesis is supported strongly by the fact that in vivo induction of CD40 signaling prevented the death of TCRδ-KO mice after infection with P. berghei XAT. This study improves our understanding of protective immunity against malaria and provides insights into γδ T-cell-mediated protective immunity against various infectious diseases.

authors

Inoue S,Niikura M,Takeo S,Mineo S,Kawakami Y,Uchida A,Kamiya S,Kobayashi F

doi

10.1073/pnas.1204480109

subject

Has Abstract

pub_date

2012-07-24 00:00:00

pages

12129-34

issue

30

eissn

0027-8424

issn

1091-6490

pii

1204480109

journal_volume

109

pub_type

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