Cutting edge: IL-16/CD4 preferentially induces Th1 cell migration: requirement of CCR5

J Immunol. 2003 Nov 15;171(10):4965-8. doi: 10.4049/jimmunol.171.10.4965.

Abstract

IL-16 binds to CD4 and induces a migratory response in CD4(+) T cells. Although it has been assumed that CD4 is the sole receptor and that IL-16 induces a comparable migratory response in all CD4(+) T cells, this has not been investigated. In this study, we determined that IL-16 preferentially induces a migratory response in Th1 cells. Because chemokine receptor CCR5 is expressed predominantly in Th1 cells and is physically associated with CD4, we investigated whether IL-16/CD4 stimulation was enhanced in the presence of CCR5. Using T cells from CCR5(null) mice, we determined that IL-16-induced migration was significantly greater in the presence of CCR5. The presence of CCR5 significantly increased IL-16 binding vs CD4 alone; however, IL-16 could not bind to CCR5 alone. Because CD4(+)CCR5(+) cells are prevalent at sites of inflammation, this intimate functional relationship likely plays a pivotal role for the recruitment and activation of Th1 cells.

Publication types

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

MeSH terms

  • Adjuvants, Immunologic / deficiency
  • Adjuvants, Immunologic / genetics
  • Adjuvants, Immunologic / physiology*
  • Animals
  • CD4 Antigens / biosynthesis
  • CD4 Antigens / genetics
  • CD4 Antigens / pharmacology*
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • Cell Adhesion / genetics
  • Cell Adhesion / immunology
  • Cell Line
  • Cells, Cultured
  • Chemotaxis, Leukocyte / genetics
  • Chemotaxis, Leukocyte / immunology*
  • Interleukin-16 / metabolism
  • Interleukin-16 / pharmacology*
  • Lymphocyte Activation / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Protein Binding / genetics
  • Protein Binding / immunology
  • Receptors, CCR5 / deficiency
  • Receptors, CCR5 / genetics
  • Receptors, CCR5 / physiology*
  • Signal Transduction / genetics
  • Signal Transduction / immunology
  • Th1 Cells / cytology*
  • Th1 Cells / immunology*
  • Th1 Cells / metabolism

Substances

  • Adjuvants, Immunologic
  • CD4 Antigens
  • Interleukin-16
  • Receptors, CCR5