Ly-6A.2 is a surface protein on T cells that may play a role in lympho
cyte activation. The regulation of Ly-6A.2 expression during T cell ly
mphopoiesis has been intriguing. It is one of the earliest markers exp
ressed on pluripotent hemopoietic stem cells and is present on both pr
imitive and mature T cells, but its expression is extinguished in the
thymus during key developmental stages. To determine whether Ly-6A.2 i
s active on developing T cells, as well as the significance of its dev
elopmental regulation, Ly-6A.2 was expressed throughout T cell develop
ment under control of the T cell-specific human CD2 enhancer in transg
enic mice. The constitutive overexpression of Ly-6A.2 in vivo led to a
marked impairment in the generation of thymocytes. Development was ar
rested at the time in thymic development when Ly-6A.2 expression is no
rmally turned off. These results indicate that the regulated expressio
n of Ly-6A.2 in thymocytes may be important for normal development. Mo
reover, these findings demonstrate that Ly-6A.2 is active in the thymi
c microenvironment.