Tissue specificity of E- and P-selectin ligands in Th1-mediated chronic inflammation

J Immunol. 1999 Nov 1;163(9):5086-93.

Abstract

The demonstrated role of E- and P-selectin ligands in the recruitment of Th1 cells raises the question of tissue specificity determination by pathogenic T cells. We took advantage of the fact that chronic Th1-mediated inflammation in the scid/scid CD4+CD45RBhigh T cell transfer model can occur at multiple tissue sites, resembling inflammatory bowel disease in the colon and psoriasis in the skin. We show that the majority of infiltrating effector T cells from psoriatic skin expresses high levels of functional P-selectin ligand (87 +/- 3%), detected by P-selectin-Ig (PIg), while a significantly smaller subset of T cells from colitic lesions expresses this ligand (24 +/- 2%). Similarly, E-selectin ligand is preferentially expressed on CD4+ T cells infiltrating the skin (24 +/- 2%), but only on very few CD4+ T cells infiltrating the colon (CIT; 1.3 +/- 0.8%). In contrast, CD4+ T cells infiltrating the skin express alpha4beta7 at a significantly lower level than CIT (mean fluorescence intensity, 28 vs 61, respectively), although, interestingly, alphaEbeta7 was expressed at high levels on both populations. Analysis of the disease-inducing potential of PIg+ and PIg- CD4+ CIT cells revealed that both populations not only express similar levels of the gut-homing molecule alpha4beta7 (mean fluorescence intensity, 50 vs 56, respectively), but do not differ in their capacity to express IFN-gamma. Furthermore, CIT depleted of cells expressing functional P-selectin ligand were able to induce colitis upon transfer, suggesting that induction of colitis in this model may be independent of E- and P-selectin. These results indicate that adhesion molecule expression and the homing pattern of inflammatory T cells are regulated by the local environment independently of their inflammatory capacity.

MeSH terms

  • Adoptive Transfer
  • Animals
  • CD4-Positive T-Lymphocytes / metabolism
  • CD4-Positive T-Lymphocytes / transplantation
  • Cell Movement / immunology
  • Chronic Disease
  • Colitis / etiology
  • Colitis / immunology
  • Colitis / metabolism
  • Colitis / pathology
  • Colon / immunology
  • Colon / metabolism*
  • Colon / pathology*
  • E-Selectin / metabolism*
  • Female
  • Immunophenotyping
  • Integrins / biosynthesis
  • L-Selectin / biosynthesis
  • Leukocyte Common Antigens / biosynthesis
  • Ligands
  • Mice
  • Mice, Inbred BALB C
  • Mice, SCID
  • Organ Specificity / immunology
  • P-Selectin / metabolism*
  • Psoriasis / immunology
  • Psoriasis / metabolism
  • Psoriasis / pathology
  • Skin / immunology
  • Skin / metabolism*
  • Skin / pathology*
  • Th1 Cells / immunology*
  • Th1 Cells / metabolism
  • Up-Regulation / immunology

Substances

  • E-Selectin
  • Integrins
  • Ligands
  • P-Selectin
  • integrin alpha4beta7
  • integrin alphaEbeta7
  • L-Selectin
  • Leukocyte Common Antigens