Abstract
CD7 and CD28 are T cell Ig superfamily molecules that share common signaling mechanisms. To determine roles CD7 and CD28 might play in peripheral lymphocyte development and function, we have generated CD7/CD28-double-deficient mice. CD7- and CD28-single-deficient and CD7/CD28-double-deficient mice had normal levels of CD4 and CD8-single-positive T cells in thymus and spleen. However, CD28-deficient mice had decreased CD4+CD25+ T cells in spleen compared with wild-type mice, and CD7/CD28-double-deficient mice had decreased numbers of CD4+CD25+ T cells in both thymus and spleen compared with both wild-type and CD28-deficient mice. Functional studies demonstrated that CD4+CD25+ T cells from CD28-deficient and CD7/CD28-double-deficient mice could mediate suppression of CD3 mAb activation of CD4+CD25- wild-type T cells, but were less potent than wild-type CD4+CD25+ T regulatory cells. Thyroiditis developed in aged CD7/CD28-double-deficient mice (>1 year) that was not seen in age-matched control mice or single CD7- or CD28-deficient mice, thus suggesting in vivo loss of T regulatory cells allowed for the development of spontaneous thyroiditis. Taken together, these data demonstrated collaborative roles for both CD7 and CD28 in determination of number and function of CD4+CD25+ T regulatory cells in the thymus and peripheral immune sites and in the development of spontaneous thyroiditis.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Aging / genetics
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Aging / immunology
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Animals
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Antibodies, Monoclonal / pharmacology
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Antigen-Presenting Cells / immunology
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Antigen-Presenting Cells / metabolism
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Antigens, CD / biosynthesis
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Antigens, CD7 / genetics
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Antigens, CD7 / physiology*
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B7-1 Antigen / biosynthesis
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B7-2 Antigen
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CD28 Antigens / genetics
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CD28 Antigens / physiology*
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CD3 Complex / pharmacology
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CD4-Positive T-Lymphocytes / cytology
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CD4-Positive T-Lymphocytes / immunology*
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CD4-Positive T-Lymphocytes / pathology
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CD8-Positive T-Lymphocytes / cytology
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Cell Division / immunology
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Concanavalin A / pharmacology
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Cytokines / biosynthesis
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Down-Regulation / genetics
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Down-Regulation / immunology
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Homeostasis / genetics
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Homeostasis / immunology*
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Immunophenotyping
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Leukocyte Count
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Lipopolysaccharides / pharmacology
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Lymphocyte Count
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Lymphopenia / genetics
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Lymphopenia / immunology
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Male
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Membrane Glycoproteins / biosynthesis
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Receptors, Interleukin-2 / biosynthesis*
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Spleen / cytology
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Spleen / immunology
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Spleen / metabolism
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Spleen / pathology
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T-Lymphocyte Subsets / cytology
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T-Lymphocyte Subsets / immunology*
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T-Lymphocyte Subsets / pathology
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Thymus Gland / immunology
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Thymus Gland / metabolism
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Thymus Gland / pathology
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Thyroiditis / genetics
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Thyroiditis / immunology*
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Thyroiditis / prevention & control*
Substances
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Antibodies, Monoclonal
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Antigens, CD
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Antigens, CD7
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B7-1 Antigen
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B7-2 Antigen
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CD28 Antigens
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CD3 Complex
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Cd86 protein, mouse
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Cytokines
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Lipopolysaccharides
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Membrane Glycoproteins
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Receptors, Interleukin-2
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Concanavalin A