Role of ICAM-1 and P-selectin expression in the development and effector function of CD4+CD25+regulatory T cells.
Dynamic regulatory mechanisms prevent autoreactive T cell activation. Upon T cell receptor crosslinking, CD4+CD25+ T regulatory (T(R)) cells block both the proliferation and cytokine production of CD4+CD25- effector cells in an apparent antigen non-specific manner. Within the T(R)population, L-selectin (CD62L)(hi)T(R)cells have been described as more efficient suppressors of T cell proliferation than CD62L(low)T(R)cells. We have previously reported that CD4+CD25+CD62L(hi)T(R)cells express elevated levels of two additional adhesion molecules, ICAM-1 (CD54) and P-selectin (CD62P) in comparison to non-T(R)cells. In the current study, we investigated the functional contribution of CD54 and CD62P expression to the suppressive phenotype of T(R)cells both in vitro and in vivo. While the CD4+CD25+ T(R)cell population was demonstrated to be significantly larger in CD62P-/- mice than in wild-type C57BL/6 mice, CD62P-/- T(R)cell function was deficient in vitro, but not in vivo. Interestingly, we detected no deficiencies in T(R)cell numbers or effector function in CD54-/- mice suggesting that T(R)cells may differ from effector CD4+ T cells in the requirement for CD54 expression within the immunological synapse. Collectively, these findings indicate that CD62P may influence T(R)cell differentiation/development and that T(R)cell activation occurs independently of CD54 expression.
Kohm
Adam P
AP
Department of Microbiology-Immunology and the Interdepartmental Immunobiology Center, Northwestern University Feinberg School of Medicine, 303 East Chicago Avenue, Chicago, IL 60611, USA.
Miller
Stephen D
SD
D019264:Adoptive Transfer; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000938:Antigen-Presenting Cells / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology / Q000378:metabolism; D017252:CD3 Complex / Q000276:immunology; D015704:CD4 Antigens / Q000032:analysis / Q000276:immunology*; D002452:Cell Count; D018920:Coculture Techniques; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000473:pathology; D005260:Female; D006023:Glycoproteins / Q000276:immunology / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000276:immunology*; D007371:Interferon-gamma / Q000378:metabolism; D007378:Interleukins / Q000378:metabolism; D019041:L-Selectin / Q000276:immunology / Q000378:metabolism; D037181:Lectins, C-Type; D008198:Lymph Nodes / Q000166:cytology; D008213:Lymphocyte Activation / Q000276:immunology; D017710:Lymphocyte Transfusion; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D063308:Myelin-Oligodendrocyte Glycoprotein; D019007:P-Selectin / Q000235:genetics / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology / Q000494:pharmacology; D015375:Receptors, Interleukin-2 / Q000032:analysis / Q000276:immunology*; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000737:chemistry / Q000187:drug effects / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000099192:CD69 Antigens
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D015704:CD4 Antigens; D006023:Glycoproteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma; D007378:Interleukins; D019041:L-Selectin; D037181:Lectins, C-Type; D063308:Myelin-Oligodendrocyte Glycoprotein; D019007:P-Selectin; D010446:Peptide Fragments; D015375:Receptors, Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D000099192:CD69 Antigens; C445081:myelin oligodendrocyte glycoprotein (35-55)