Unaltered phenotype, tissue distribution and function of V alpha 14(+) NKTcells in germ-free mice

The expression pattern of mouse CD1d and the tissue distribution of CD1d-re stricted V alpha 14-J alpha 281 NKT cells suggest that the liver and the ma rginal zone of the spleen might be preferred sites of activation of this po tent innate pathway of early cytokine secretion. Because these tissues are particularly involved with the filtration of blood-borne pathogens, and bec ause NKT cells with an activated/memory phenotype accumulate over the first weeks of life and their CD1 ligands bind microbial glycolipids, it has bee n hypothesized that expansion of the NKT cell subset may be driven by expos ure to the microbial environment. To test this hypothesis, we analyzed the frequency, surface phenotype and functional properties of NKT cells in norm al and in germ-free C57BL/6 mice. Surprisingly, we found that the NKT cell subset develops in the presence or absence of a microbial environment. Alth ough these results do not rule out the possibility that NKT cells exert a p rotective function against some microbial agents, they demonstrate that non microbial ligands, possibly self-antigens are sufficient for the generatio n, maturation and peripheral accumulation of NKT cells.