Dendritic cells support sequential reprogramming of chemoattractant receptor profiles during naive to effector T cell differentiation

J Immunol. 2003 Jul 1;171(1):152-8. doi: 10.4049/jimmunol.171.1.152.

Abstract

T cells undergo chemokine receptor switches during activation and differentiation in secondary lymphoid tissues. Here we present evidence that dendritic cells can induce changes in T cell expression of chemokine receptors in two continuous steps. In the first switch over a 4-5 day period, dendritic cells up-regulate T cell expression of CXCR3 and CXCR5. Additional stimulation leads to the second switch: down-regulation of lymphoid tissue homing related CCR7 and CXCR5, and up-regulation of Th1/2 effector tissue-targeting chemoattractant receptors such as CCR4, CCR5, CXCR6, and CRTH2. We show that IL-4 and IL-12 can determine the fate of the secondary chemokine receptor switch. IL-4 enhances the generation of CCR4(+) and CRTH2(+) T cells, and suppresses the generation of CXCR3(+) T cells and CCR7(-) T cells, while IL-12 suppresses the level of CCR4 in responding T cells. Furthermore, IL-4 has positive effects on generation of CXCR5(+) and CCR7(+) T cells during the second switch. Our study suggests that the sequential switches in chemokine receptor expression occur during naive T cell interaction with dendritic cells. The first switch of T cell chemokine receptor expression is consistent with the fact that activated T cells migrate within lymphoid tissues for interaction with B and dendritic cells, while the second switch predicts the trafficking behavior of effector T cells away from lymphoid tissues to effector tissue sites.

Publication types

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

MeSH terms

  • Cell Communication / immunology
  • Cell Differentiation / immunology
  • Cells, Cultured
  • Coculture Techniques
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism*
  • Humans
  • Immunologic Memory
  • Interleukin-12 / metabolism
  • Interleukin-12 / physiology
  • Interleukin-4 / metabolism
  • Interleukin-4 / physiology
  • Interphase / immunology*
  • Lymphocyte Activation / immunology*
  • Lymphocyte Count
  • Receptors, Chemokine / biosynthesis*
  • T-Lymphocyte Subsets / cytology
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism*
  • Th1 Cells / cytology
  • Th2 Cells / cytology
  • Time Factors
  • Up-Regulation / immunology*

Substances

  • Receptors, Chemokine
  • Interleukin-12
  • Interleukin-4
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