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

Experimental infection of C57BL/6 mice by Plasmonium yoelii sporozoites induced an increase of CD4(-)CD8(-) NK1.1(+) TCR alpha beta(int) cells and a down-regulation of CD4(+) NK1.1(+) TCR alpha beta(int) cells in the liver during the acute phase of the infection. These cells showed an activated CD69(+), CD122(+), CD44(high), and CD62L(high) surface phenotype. Analysis of the expressed TCRV beta segment repertoire revealed that most of the expanded CD4-CD8- (double-negative) T cells presented a skewed TCRV beta repertoire and preferentially used V beta 2 and V beta 7 rather than vps, 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-gamma was in part involved in this antiparasite activity. These results suggest that up-regulation of CD4(-)CD8(-) NK1.1(+) alpha beta T cells and down-regulation of CD4(+) NK1.1(+) TCR alpha beta(int) cells may contribute to the early immune response induced by the Plasmodium during the prime infection.