Differential regulation of Ly49 expression on CD4(+) and CD4(-)CD8(-) (double negative) NK1.1(+) T cells

The pan-NK cell marker NK1.1, present in some mouse strains, is also found on a subset of TCR alpha beta(+) lymphocytes termed NKT cells. These cells are primarily CD4(+) or CD4(-)CD8(-) (double negative, DN), and both NKT su bpopulations contain cells reactive with the MHC class I-like molecule CD1d . Murine NK cells express clonally distributed inhibitory receptors of the Ly49 family that bind to different alleles of MHC class I molecules and tra nsmit negative signals regulating NK cell function. Ly49 receptors are also found on TCR alpha beta(+) NK1.1(+) T cells. To investigate the potential role of inhibitory Ly49 markers in the regulation of NKT cells, we have don e a thorough analysis of their expression on different NKT populations. The CD4(+) and DN NK1.1(+) T cell subsets have traditionally been dealt with a s one NK1.1(+) T cell population, but we found dramatic differences between these two NKT cell subsets. We demonstrate here expression of Ly49 recepto rs on DN, but not on CD4(+), NK1.1(+) T cells in spleen and liver. Absence of the specific MHC class I ligand in the host was associated with elevated levels of expression and, to a greater extent than has been found for NK c ells, increased the frequencies of Ly49-positive cells within the DN subset , while CD4(+) NK1.1(+) cells remained negative. In the thymus and bone mar row both NK1.1(+) T cell subsets contained high frequencies of Ly49-positiv e cells. Results from in vitro stimulation of DN NKT cells further suggest that activation and expansion of NKT cell subsets are regulated by the Ly49 receptors.