Tissue specificity of E- and P-selectin ligands in Th1-mediated chronic inflammation.
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.
Chu
A
A
Protein Design Laboratories, Inc., Fremont, CA 94555, USA.
Hong
K
K
Berg
E L
EL
Ehrhardt
R O
RO
D019264:Adoptive Transfer; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism / Q000637:transplantation; D002465:Cell Movement / Q000276:immunology; D002908:Chronic Disease; D003092:Colitis / Q000209:etiology / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D003106:Colon / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D019040:E-Selectin / Q000378:metabolism*; D005260:Female; D016130:Immunophenotyping; D016023:Integrins / Q000096:biosynthesis; D019041:L-Selectin / Q000096:biosynthesis; D017493:Leukocyte Common Antigens / Q000096:biosynthesis; D008024:Ligands; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D009928:Organ Specificity / Q000276:immunology; D019007:P-Selectin / Q000378:metabolism*; D011565:Psoriasis / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D012867:Skin / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism; D015854:Up-Regulation / Q000276:immunology
D019040:E-Selectin; D016023:Integrins; D008024:Ligands; D019007:P-Selectin; C071777:integrin alpha4beta7; C070709:integrin alphaEbeta7; D019041:L-Selectin; D017493:Leukocyte Common Antigens