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-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.

[1]  C. Mackay,et al.  The HIV coreceptors CXCR4 and CCR5 are differentially expressed and regulated on human T lymphocytes. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[2]  T. Geiser,et al.  Cloning of a human seven-transmembrane domain receptor, LESTR, that is highly expressed in leukocytes. , 1994, The Journal of biological chemistry.

[3]  N. Copeland,et al.  TECK: a novel CC chemokine specifically expressed by thymic dendritic cells and potentially involved in T cell development. , 1997, Immunity.

[4]  W. Swat,et al.  Small CD4+8+TCRlow thymocytes contain precursors of mature T cells , 1994, European journal of immunology.

[5]  I. Weinstein,et al.  Molecular cloning of TPAR1, a gene whose expression is repressed by the tumor promoter 12-O-tetradecanoylphorbol 13-acetate (TPA). , 1994, Experimental cell research.

[6]  T. Honjo,et al.  Signal sequence trap: a cloning strategy for secreted proteins and type I membrane proteins. , 1993, Science.

[7]  Jean Salamero,et al.  HIV Coreceptor Downregulation as Antiviral Principle: SDF-1α–dependent Internalization of the Chemokine Receptor CXCR4 Contributes to Inhibition of HIV Replication , 1997, The Journal of experimental medicine.

[8]  D. Taub,et al.  Chemokines regulate T cell adherence to recombinant adhesion molecules and extracellular matrix proteins. , 1996, Journal of immunology.

[9]  T. Springer,et al.  A highly efficacious lymphocyte chemoattractant, stromal cell-derived factor 1 (SDF-1) , 1996, The Journal of experimental medicine.

[10]  C. Mackay,et al.  Biology of chemokine and classical chemoattractant receptors: differential requirements for adhesion-triggering versus chemotactic responses in lymphoid cells , 1996, The Journal of cell biology.

[11]  J. Sprent,et al.  Thymic selection and cell division , 1995, The Journal of experimental medicine.

[12]  Allen D. Delaney,et al.  Molecular cloning of the cDNA and chromosomal localization of the gene for a putative seven-transmembrane segment (7-TMS) receptor isolated from human spleen. , 1993, Genomics.

[13]  T. Springer,et al.  Molecular cloning and characterization of a murine pre-B-cell growth-stimulating factor/stromal cell-derived factor 1 receptor, a murine homolog of the human immunodeficiency virus 1 entry coreceptor fusin. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[14]  N. Yoshida,et al.  CXCR4/fusin Is Not a Species-specific Barrier in Murine Cells for HIV-1 Entry , 1997, The Journal of experimental medicine.

[15]  H. Kikutani,et al.  Molecular cloning and structure of a pre-B-cell growth-stimulating factor. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[16]  K. Matsushima,et al.  Molecular cloning of cDNAs encoding a LD78 receptor and putative leukocyte chemotactic peptide receptors. , 1993, International immunology.

[17]  M. Murakami,et al.  Long‐Term Acceptance of Major Histocompatibility Complex‐Mismatched Cardiac Allograft Induced by a Low Dose of CTLA4IgM Plus FK506 , 1996, Microbiology and immunology.

[18]  J. D. Benson,et al.  Cloning of the mouse fusin gene, homologue to a human HIV-1 co-factor. , 1996, Journal of immunology.

[19]  J. Inazawa,et al.  Structure and chromosomal localization of the human stromal cell-derived factor 1 (SDF1) gene. , 1995, Genomics.

[20]  R. Horuk.  The interleukin-8-receptor family: from chemokines to malaria. , 1994, Immunology today.

[21]  R. Doms,et al.  CD4-Independent Infection by HIV-2 Is Mediated by Fusin/CXCR4 , 1996, Cell.

[22]  K. Shortman,et al.  Small cortical thymocytes are subject to positive selection , 1994, The Journal of experimental medicine.

[23]  Paul E. Kennedy,et al.  HIV-1 Entry Cofactor: Functional cDNA Cloning of a Seven-Transmembrane, G Protein-Coupled Receptor , 1996, Science.

[24]  T. Nakayama,et al.  CD69 cell surface expression identifies developing thymocytes which audition for T cell antigen receptor-mediated positive selection. , 1993, International immunology.

[25]  S. Nishikawa,et al.  Defects of B-cell lymphopoiesis and bone-marrow myelopoiesis in mice lacking the CXC chemokine PBSF/SDF-1 , 1996, Nature.

[26]  T. Springer,et al.  The C–C Chemokine MCP-1 Differentially Modulates the Avidity of β1 and β2 Integrins on T Lymphocytes , 1996 .