CD7 and CD28 are required for murine CD4+CD25+ regulatory T cell homeostasis and prevention of thyroiditis.
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.
Sempowski
Gregory D
GD
Department of Medicine and the Duke University Human Vaccine Institute, Duke University Medical Center, Box 3258, Research Park Building 1, Room 113, Research Drive, Durham, NC 27710, USA. gsem@acpub.duke.edu
Cross
Scott J
SJ
Heinly
Craig S
CS
Scearce
Richard M
RM
Haynes
Barton F
BF
D000375:Aging / Q000235:genetics / Q000276:immunology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D015703:Antigens, CD / Q000096:biosynthesis; D019011:Antigens, CD7 / Q000235:genetics / Q000502:physiology*; D018122:B7-1 Antigen / Q000096:biosynthesis; D051940:B7-2 Antigen; D018106:CD28 Antigens / Q000235:genetics / Q000502:physiology*; D017252:CD3 Complex / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology; D002455:Cell Division / Q000276:immunology; D003208:Concanavalin A / Q000494:pharmacology; D016207:Cytokines / Q000096:biosynthesis; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology; D006706:Homeostasis / Q000235:genetics / Q000276:immunology*; D016130:Immunophenotyping; D007958:Leukocyte Count; D008070:Lipopolysaccharides / Q000494:pharmacology; D018655:Lymphocyte Count; D008231:Lymphopenia / Q000235:genetics / Q000276:immunology; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis*; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000473:pathology; D013950:Thymus Gland / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D013966:Thyroiditis / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D019011:Antigens, CD7; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D018106:CD28 Antigens; D017252:CD3 Complex; C497965:Cd86 protein, mouse; D016207:Cytokines; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D015375:Receptors, Interleukin-2; D003208:Concanavalin A