Resistance to Malarial Infection Is Achieved by the Cooperation of NK1.1 super(+) and NK1.1 super(-) Subsets of Intermediate TCR Cells Which Are Constituents of Innate Immunity

We previously reported that the major expanding lymphocytes were intermediate TCR (TCR super(int)) cells (mainly NK1.1 super(-)) during malarial infection in mice. Cell transfer experiments of TCR super(int) cells indicated that these T cells mediated resistance to malaria. However, TCR super(int) cells always contain NK1.1 super(+)TCR super(int) cells (i.e., NKT cells) and controversial results (NKT cells were effective or not for resistance to malaria) have been reported by different investigators. In this study, we used CD1d super((-/-)) mice, which almost completely lack NKT cells in the liver and other immune organs. Parasitemia was prolonged in the blood of CD1d super((- /-)) mice and the expansion of lymphocytes in the liver of these mice was more prominent after an injection of Plasmodium yoelii-infected erythrocytes. However, these mice finally recovered from malaria. In contrast to B6 mice, CD4 super(-)8 super(-) NKT cells as well as NK1.1 super(-)CD3 super(int) cells expanded in CD1d super((- /-)) mice after malarial infection, instead of CD4 super(+) (and CD8 super(+)) NKT cells. These newly generated CD4 super(-)8 super(-)NKT cells in CD1d super((-/-)) mice did not use an invariant chain of V alpha 14J alpha 281 for TCR alpha . Other evidence was that severe thymic atrophy and autoantibody production were accompanied by malarial infection, irrespective of the mice used. These results suggest that both NK1.1 super(-) and NK1.1 super(+) subsets of TCR super(int) cells (i.e., constituents of innate immunity) are associated with resistance to malaria and that an autoimmune-like state is induced during malarial infection. Copyright 2001 Academic Press.