Murine CCR9, a chemokine receptor for thymus-expressed chemokine that is up-regulated following pre-TCR signaling

J Immunol. 2000 Jan 15;164(2):639-48. doi: 10.4049/jimmunol.164.2.639.

Abstract

Chemokines are likely to play an important role in regulating the trafficking of developing T cells within the thymus. By using anti-CD3varepsilon treatment of recombinase-activating gene 2 (Rag2-/-) mice to mimic pre-TCR signaling and drive thymocyte development to the double positive stage, we have identified murine GPR-9-6 as a chemokine receptor whose expression is strongly induced following pre-TCR signaling. GPR-9-6 mRNA is present at high levels in the thymus, and by RT-PCR analysis its expression is induced as normal thymocytes undergo the double negative to double positive transition. Furthermore we show that TECK (thymus-expressed chemokine), a chemokine produced by thymic medullary dendritic cells, is a functional ligand for GPR-9-6. TECK specifically induces a calcium flux and chemotaxis of GPR-9-6-transfected cells. In addition, TECK stimulates the migration of normal double positive thymocytes, as well as Rag2-/- thymocytes following anti-CD3varepsilon treatment. Hence, GPR-9-6 has been designated as CC chemokine receptor 9 (CCR9). Our results suggest that TECK delivers signals through CCR9 important for the navigation of developing thymocytes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacology
  • Calcium / metabolism
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology
  • Cell Line
  • Cell Movement / immunology
  • Chemokines, CC / metabolism*
  • Chemokines, CC / physiology
  • Chemotaxis, Leukocyte / immunology
  • DNA-Binding Proteins / deficiency
  • DNA-Binding Proteins / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Receptors, Antigen, T-Cell / immunology
  • Receptors, Antigen, T-Cell / physiology*
  • Receptors, CCR
  • Receptors, Chemokine / biosynthesis*
  • Receptors, Chemokine / genetics
  • Signal Transduction / immunology*
  • Stem Cells / metabolism*
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism
  • Thymus Gland / cytology
  • Thymus Gland / metabolism*
  • Transfection
  • Up-Regulation / immunology*

Substances

  • Antibodies, Monoclonal
  • CC chemokine receptor 9
  • Ccl25 protein, mouse
  • Chemokines, CC
  • DNA-Binding Proteins
  • Rag2 protein, mouse
  • Receptors, Antigen, T-Cell
  • Receptors, CCR
  • Receptors, Chemokine
  • V(D)J recombination activating protein 2
  • antigen T cell receptor, epsilon chain
  • Calcium