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 chemokines that are induced by inflammation, SDF-1 is constitutively produced by stromal cells, In order to investigate the physiological roles of SDF-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 double-positive (DP) cell stage, Interestingly, SDF-1R expression was down-modulated after positive selection; CD69(+)CD3(hl) DP and CD3(hl) single-positive thymocytes were SDF-1R(-/lo). Northern blot analysis demonstrated that SDF-1 and CXCR4 mRNAs were abundantly expressed in the thymuses of embryo and adult mice, These results demonstrate that SDF-1R expression is involved in T cell development in the thymus, particularly in positive selection.