Loss of SDF-1 receptor expression during positive selection in the thymus

• Published in: International immunology Vol. 10; no. 8; pp. 1049 - 1056
• Main Authors: Suzuki, G, Nakata, Y, Dan, Y, Uzawa, A, Nakagawa, K, Saito, T, Mita, K, Shirasawa, T
• Format: Journal Article
• Language: English
• Published: England Oxford Publishing Limited (England) 01.08.1998
• Subjects: Animals; Antigens, CD - immunology; Binding Sites; Binding, Competitive; Blotting, Northern; Bone Marrow - embryology; Bone Marrow - immunology; Chemokine CXCL12; Chemokines, CXC - genetics; Chemokines, CXC - metabolism; Down-Regulation; Flow Cytometry; Hematopoietic Stem Cells - immunology; Humans; Immunoglobulin gamma-Chains - genetics; Immunoglobulin gamma-Chains - metabolism; Liver - embryology; Liver - immunology; Lymphoma; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Organ Specificity - genetics; Proto-Oncogene Proteins c-kit - immunology; Receptors, CXCR4 - genetics; Receptors, CXCR4 - metabolism; Recombinant Fusion Proteins - genetics; Recombinant Fusion Proteins - metabolism; Recombinant Proteins - metabolism; T-Lymphocyte Subsets - immunology; Thymus Gland - embryology; Thymus Gland - immunology; Tumor Cells, Cultured
• ISSN: 0953-8178; 1460-2377; 1460-2377
• DOI: 10.1093/intimm/10.8.1049

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-Cgamma1, composed from murine SDF-1alpha and the constant region of human IgG. SDF-1-Cgamma1 stained EL-4 T lymphoma cells and the staining was blocked by rhSDF-1beta. 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+CD3hi DP and CD3hi 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.