Ly49 receptors are inhibitory receptors expressed on subsets of both NK cel
ls and NK1.1(+) T cells. The function of these receptors on NK cells is bel
ieved to be important in maintaining self-tolerance, yet their role on T ce
lls is unclear. in this report we investigated how an Ly49A transgene alter
s T and NK cell development in an in vivo environment, where a ligand for L
y49A is expressed. Ly49A transgenic mice that co-expressed an MHC ligand fo
r Ly49A, H-2D(d), developed a severe inflammatory disorder that resulted in
death within the first weeks of age. T cells expressing forbidden TCR V-be
ta chains were found both in the thymus and periphery of transgenic mice, w
hile non-transgenic littermates had successfully deleted these T cell subse
ts. These data indicate that the expression of Ly49A on T cells could alter
T cell selection and allow survival of potentially self-reactive T cells.