LOSS OF SDF-1 RECEPTOR EXPRESSION DURING POSITIVE SELECTION IN THE THYMUS

SDF-1 is a member of the CXC chemokines. In contrast to other chemokin es that are induced by inflammation, SDF-1 is constitutively produced by stromal cells, In order to investigate the physiological roles of S DF-1, we constructed a fusion protein, SDF-1-C(gamma)1, composed from murine SDF-1 alpha and the constant region of human IgG. SDF-1-C(gamma )1 stained EL-4 T lymphoma cells and the staining was blocked by rhSDF -1 beta, The expression levels of SDF-1R altered along with the T cell maturation. Most c-kit(+) hematopoietic precursors in fetal liver in gestational day (GD) 14.5 embryo were SDF-1R(-), while c-kit(+) double -negative (DN) thymocytes in the embryo were positive for SDF-1R, The receptor expression increased along with T cell maturation up to doubl e-positive (DP) cell stage, Interestingly, SDF-1R expression was down- modulated after positive selection; CD69(+)CD3(hl) DP and CD3(hl) sing le-positive thymocytes were SDF-1R(-/lo). Northern blot analysis demon strated that SDF-1 and CXCR4 mRNAs were abundantly expressed in the th ymuses of embryo and adult mice, These results demonstrate that SDF-1R expression is involved in T cell development in the thymus, particula rly in positive selection.