Liver CD4 super(-)CD8 super(-) NK1.1 super(+) TCR alpha beta Intermediate Cells Increase During Experimental Malaria Infection and Are Able to Exhibit Inhibitory Activity Against the Parasite Liver Stage In Vitro

Experimental infection of C57BL/6 mice by Plasmodium yoelii sporozoites induced an increase of CD4 super(-)CD8 super(-) NK1.1 super(+) TCR alpha beta super(int) cells and a down-regulation of CD4 super(+) NK1.1 super(+) TCR alpha beta super(int) cells in the liver during the acute phase of the infection. These cells showed an activated CD69 super(+), CD122 super(+), CD44 super(high), and CD62L super(high) surface phenotype. Analysis of the expressed TCRV beta segment repertoire revealed that most of the expanded CD4 super(-)CD8 super(-) (double-negative) T cells presented a skewed TCRV beta repertoire and preferentially used V beta 2 and V beta 7 rather than V beta 8. To get an insight into the function of expanded NK1.1 super(+) T cells, experiments were designed in vitro to study their activity against P. yoelii liver stage development. P. yoelii-primed CD3 super(+) NK1.1 super(+) intrahepatic lymphocytes inhibited parasite growth within the hepatocyte. The antiplasmodial effector function of the parasite-induced NK1.1 super(+) liver T cells was almost totally reversed with an anti-CD3 Ab. Moreover, IFN- gamma was in part involved in this antiparasite activity. These results suggest that up-regulation of CD4 super(-)CD8 super(-) NK1.1 super(+) alpha beta T cells and down-regulation of CD4 super(+) NK1.1 super(+) TCR alpha beta super(int) cells may contribute to the early immune response induced by the Plasmodium during the prime infection.