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

Int Immunol. 1998 Aug;10(8):1049-56. doi: 10.1093/intimm/10.8.1049.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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

Substances

  • Antigens, CD
  • CXCL12 protein, human
  • Chemokine CXCL12
  • Chemokines, CXC
  • Cxcl12 protein, mouse
  • Immunoglobulin gamma-Chains
  • Receptors, CXCR4
  • Recombinant Fusion Proteins
  • Recombinant Proteins
  • Proto-Oncogene Proteins c-kit