Liver CD4−CD8− NK1.1+ TCRαβ Intermediate Cells Increase During Experimental Malaria Infection and Are Able to Exhibit Inhibitory Activity Against the Parasite Liver Stage In Vitro

Abstract

Experimental infection of C57BL/6 mice by Plasmodium  yoelii sporozoites induced an increase of CD4−CD8− NK1.1+ TCRαβint cells and a down-regulation of CD4+ NK1.1+ TCRαβint cells in the liver during the acute phase of the infection. These cells showed an activated CD69+, CD122+, CD44high, and CD62Lhigh surface phenotype. Analysis of the expressed TCRVβ segment repertoire revealed that most of the expanded CD4−CD8− (double-negative) T cells presented a skewed TCRVβ repertoire and preferentially used Vβ2 and Vβ7 rather than Vβ8. To get an insight into the function of expanded NK1.1+ T cells, experiments were designed in vitro to study their activity against P. yoelii liver stage development. P. yoelii-primed CD3+ NK1.1+ intrahepatic lymphocytes inhibited parasite growth within the hepatocyte. The antiplasmodial effector function of the parasite-induced NK1.1+ liver T cells was almost totally reversed with an anti-CD3 Ab. Moreover, IFN-γ was in part involved in this antiparasite activity. These results suggest that up-regulation of CD4−CD8− NK1.1+ αβ T cells and down-regulation of CD4+ NK1.1+ TCRαβint cells may contribute to the early immune response induced by the Plasmodium during the prime infection.