Resistance to malarial infection is achieved by the cooperation of NK1.1(+) and NK1.1(-) subsets of intermediate TCR cells which are constituents of innate immunity

We previously reported that the major expanding lymphocytes were intermedia te TCR (TCRint) cells (mainly NK1.1(-)) during malarial infection in mice. Cell transfer experiments of TCRint cells indicated that these T cells medi ated resistance to malaria. However, TCRint cells always contain NK1.1(+)TC R(int) cells (i.e., NKT cells) and controversial results (NKT cells were ef fective or not for resistance to malaria) have been reported by different i nvestigators. In this study, we used CD1d((-/-)) mice, which almost complet ely lack NKT cells in the liver and other immune organs. Parasitemia was pr olonged in the blood of CD1d((-/-)) mice and the expansion of lymphocytes i n the liver of these mice was more prominent after an injection of Plasmodi um yoelii-infected erythrocytes. However, these mice finally recovered from malaria. In contrast to B6 mice, CD4(-)8(-) NKT cells as well as NK1.1(-)C D3(int) cells expanded in CD1d((-/-)) mice after malarial infection, instea d of CD4(+) (and CD8(+)) NKT cells. These newly generated CD4(-)8(-)NKT cel ls in CD1d((-/-)) mice did not use an invariant chain of V alpha 14J alpha 281 for TCR alpha. Other evidence was that severe thymic atrophy and autoan tibody production were accompanied by malarial infection, irrespective of t he mice used. These results suggest that both NK1.1- and NK1.1(+) subsets o f TCRint cells (i.e., constituents of innate immunity) are associated with resistance to malaria and that an autoimmune-like state is induced during m alarial infection. (C) 2001 Academic Press.