Negative regulation of T-cell adhesion and activation by CD43.
CD43 is a cell-surface sialoglycoprotein expressed by a variety of haematopoietically derived cells, including T lymphocytes. Earlier observations of defective CD43 expression by T lymphocytes from boys with the X-chromosome-linked Wiskott-Aldrich syndrome suggested the importance of CD43 in lymphocyte function. Subsequent studies have suggested that CD43 facilitates leukocyte adhesion and has a co-stimulatory role during T-cell activation. To define the physiologically relevant function(s) of CD43, we have generated CD43-knockout mice. We report here that CD43-deficient T cells from such mice show a marked increase in their in vitro proliferative response to concanavalin A, anti-CD3, the superantigen SEB and allostimulation. Additionally, CD43-deficient T cells show a substantial enhancement in homotypic adhesion and in their ability to bind different ligands, including fibronectin and the intercellular adhesion molecule ICAM-1. Vaccinia-virus-infected CD43-knockout mice mounted an augmented anti-vaccinia cytotoxic T-cell response compared with their wild-type littermates, yet developed an increased virus load. We conclude that CD43 negatively regulates T-cell activation and adhesion and is important for viral clearance.
Manjunath
N
N
Department of Medicine, New England Medical Center Hospitals, Boston, Massachusetts 02111, USA.
Correa
M
M
Ardman
M
M
Ardman
B
B
D000818:Animals; D015703:Antigens, CD; D002448:Cell Adhesion; D002460:Cell Line; D003208:Concanavalin A / Q000276:immunology; D005353:Fibronectins / Q000378:metabolism; D006410:Hematopoiesis / Q000502:physiology; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D051917:Leukosialin; D008024:Ligands; D008213:Lymphocyte Activation; D051379:Mice; D018345:Mice, Knockout; D018847:Opioid Peptides / Q000737:chemistry / Q000302:isolation & purification* / Q000502:physiology; D012795:Sialoglycoproteins / Q000276:immunology*; D018089:Superantigens / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014615:Vaccinia / Q000276:immunology; D000097629:Nociceptin
D015703:Antigens, CD; D003208:Concanavalin A; D005353:Fibronectins; D018799:Intercellular Adhesion Molecule-1; D051917:Leukosialin; D008024:Ligands; D018847:Opioid Peptides; D012795:Sialoglycoproteins; D018089:Superantigens; D000097629:Nociceptin; C497863:Spn protein, mouse