Negative regulation of T-cell adhesion and activation by CD43

Abstract

CD43 is a cell-surface sialoglycoprotein expressed by a variety of haematopoietically derived cells, including T lymphocytes^1á¤-9. Earlier observations of defective CD43 expression by ? lymphocytes from boys with the X-chromosome-linked Wiskottá¤-Aldrich syndrome suggested the importance of CD43 in lymphocyte function^10,11. Subsequent studies have suggested that CD43 facilitates leukocyte adhesion^12á¤-14 and has a co-stimulatory role during T-cell activation¹⁵. 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 concana-valin A, anti-CD3, the superantigen SEB and allostimulation. Additionally, CD43-deficient ? 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.