Abstract
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.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adoptive Transfer
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Animals
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Antibodies, Monoclonal / pharmacology
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Antigen-Presenting Cells / immunology
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Antigens, CD / immunology
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Antigens, CD / metabolism
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Antigens, Differentiation, T-Lymphocyte / immunology
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Antigens, Differentiation, T-Lymphocyte / metabolism
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CD3 Complex / immunology
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CD4 Antigens / analysis
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CD4 Antigens / immunology*
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Cell Count
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Coculture Techniques
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Encephalomyelitis, Autoimmune, Experimental / immunology
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Encephalomyelitis, Autoimmune, Experimental / pathology
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Female
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Glycoproteins / immunology
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Glycoproteins / pharmacology
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Granulocyte-Macrophage Colony-Stimulating Factor / metabolism
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Intercellular Adhesion Molecule-1 / genetics
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Intercellular Adhesion Molecule-1 / immunology*
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Interferon-gamma / metabolism
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Interleukins / metabolism
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L-Selectin / immunology
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L-Selectin / metabolism
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Lectins, C-Type
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Lymph Nodes / cytology
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Lymphocyte Activation / immunology
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Lymphocyte Transfusion
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Myelin-Oligodendrocyte Glycoprotein
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P-Selectin / genetics
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P-Selectin / immunology*
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Peptide Fragments / immunology
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Peptide Fragments / pharmacology
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Receptors, Interleukin-2 / analysis
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Receptors, Interleukin-2 / immunology*
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Spleen / cytology
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T-Lymphocytes / chemistry
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T-Lymphocytes / drug effects
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T-Lymphocytes / immunology*
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Th1 Cells / immunology
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Tumor Necrosis Factor-alpha / metabolism
Substances
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Antibodies, Monoclonal
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Antigens, CD
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Antigens, Differentiation, T-Lymphocyte
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CD3 Complex
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CD4 Antigens
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CD69 antigen
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Glycoproteins
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Interleukins
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Lectins, C-Type
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Myelin-Oligodendrocyte Glycoprotein
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P-Selectin
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Peptide Fragments
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Receptors, Interleukin-2
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Tumor Necrosis Factor-alpha
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myelin oligodendrocyte glycoprotein (35-55)
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Intercellular Adhesion Molecule-1
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L-Selectin
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Interferon-gamma
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Granulocyte-Macrophage Colony-Stimulating Factor