Enhancement of dendritic cell activation via CD40 ligand-expressing γδ T cells is responsible for protective immunity to Plasmodium parasites.
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.
Department of Infectious Diseases, Kyorin University School of Medicine, Tokyo, Japan.
Shin-Ichi
S
Inoue
Mamoru
M
Niikura
Satoru
S
Takeo
Shoichiro
S
Mineo
Yasushi
Y
Kawakami
Akihiko
A
Uchida
Shigeru
S
Kamiya
Fumie
F
Kobayashi
D000818:Animals; D000911:Antibodies, Monoclonal; D023201:CD40 Ligand / Q000276:immunology*; D016207:Cytokines / Q000097:blood; D003713:Dendritic Cells / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007150:Immunohistochemistry; D007167:Immunotherapy / Q000379:methods*; D007371:Interferon-gamma / Q000097:blood; D008288:Malaria / Q000276:immunology* / Q000517:prevention & control; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018512:Parasitemia; D010962:Plasmodium berghei / Q000276:immunology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D016207:Cytokines; D016692:Receptors, Antigen, T-Cell, gamma-delta; D023201:CD40 Ligand; D007371:Interferon-gamma