NEGATIVE REGULATION OF T-CELL ADHESION AND ACTIVATION BY CD43

CD43 is a cell-surface sialoglycoprotein expressed by a variety of hae matopoietically derived cells, including T lymphocytes(1-9). Earlier o bservations of defective CD43 expression by T lymphocytes from boys wi th the X-chromosome-linked Wiskott-Aldrich syndrome suggested the impo rtance of CD43 in lymphocyte function(10,11). Subsequent studies have suggested that CD43 facilitates leukocyte adhesion(12-14) and has a co -stimulatory role during T-cell activation(15). To define the physiolo gically relevant functions(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 concanav alin A, anti-CD3, the superantigen SEB and allostimulation. Additional ly, CD43-deficient T cells show a substantial enhancement in homotypic adhesion and in their ability to bind different ligands, including fi bronectin and the intercellular adhesion molecule ICAM-1. Vaccinia-vir us-infected CD43-knockout mice mounted an augmented anti-vaccinia, cyt otoxic T-cell response compared with their wild-type littermates, yet developed an increased virus load. We conclude that CD43 negatively re gulates T-cell activation and adhesion and is important for viral clea rance.