Long-term commitment to inflammation-seeking homing in CD4+ effector cells

J Immunol. 2007 Jun 15;178(12):8073-80. doi: 10.4049/jimmunol.178.12.8073.

Abstract

Access of T effector cells to sites of inflammation is a prerequisite for an efficient action in immune defense and is mediated by different, partly tissue-specific sets of adhesion molecules. To what extent lymphocytes memorize the site of initial priming and develop organ-specific homing properties is still a matter of debate. Notably, data on the stability of homing receptor expression on T cells in vivo are largely lacking. We approached this question by the adoptive transfer of CD4(+) T cells sorted for the expression of P-selectin ligands, which contribute to migration into inflamed sites in skin and other tissues. We observed long-term expression of P-selectin ligands on roughly one-third of effector cells. On those cells that had lost P-selectin ligands, re-expression upon Ag challenge was observed but only within pLNs, similar to the organ-selective induction upon the primary activation of naive T cells. The frequency of cells stably expressing P-selectin ligands was higher when cells were repeatedly stimulated under permissive conditions in the presence of IL-12, indicating a gradual fixation of this phenotype. In line with that finding, isolated P-selectin ligand positive memory T cells showed the highest frequency of long-term expressing cells. A tissue-specific environment was not required for the long-term maintenance of P-selectin ligand expression on the subfraction of effector cells. These data indicate that the expression of selectin ligands can become clonally imprinted under certain conditions, but also that a major fraction of the cells remains flexible and subject to environmental modulation upon restimulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / chemistry
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / immunology*
  • Cell Movement
  • Cells, Cultured
  • Dermatitis / immunology*
  • Immunologic Memory
  • Inflammation / immunology
  • Integrins / analysis
  • Integrins / metabolism*
  • Membrane Glycoproteins / analysis
  • Membrane Glycoproteins / metabolism*
  • Mice
  • T-Lymphocyte Subsets / chemistry
  • T-Lymphocyte Subsets / drug effects
  • T-Lymphocyte Subsets / immunology*
  • Tretinoin / pharmacology

Substances

  • Integrins
  • Membrane Glycoproteins
  • P-selectin ligand protein
  • integrin alpha4beta7
  • Tretinoin