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. 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.

Dynamic Regulation of T Cell Immunity by CD43

“…We propose that, depending on the state of activation of the T cell, CD43 may have positive or negative regulatory roles during an immune response. On a naive T cell, the 115-kDa glycoform is abundantly sialylated, and this large negatively charged glycoprotein seems to play a negative regulatory role in T cell homing (9) and activation in vitro (8). However, our work suggests that, on activated T cells, CD43 and other cell surface glycoproteins become hyposialylated.…”

“…Cross-linking CD43 has been shown to play a role in the costimulation of T cells in vitro (12); however, CD43 Ϫ/Ϫ T cells have been shown to be hyperproliferative in vitro (8,13). We examined the CD8 T cell response on day 8 in CD43…”

“…Additionally, CD43 has been shown to play a role in T cell activation, although this, too, remains unclear. Ab cross-linking experiments suggested a costimulatory role in vitro (12); however, other groups suggested a negative regulatory role in T cell activation (8,13). Most recently, it has been shown that CD43 is excluded from the immunological synapse during T cell activation, and this exclusion appears to be mediated by an ezrinradixin-moesin-dependent mechanism(s) (14 -17).…”

Molecular cloning of Porimin, a novel cell surface receptor mediating oncotic cell death

“…Although mucins mainly affect cell adhesion and ligand binding, several membrane mucins have also been documented to trigger cell death or inhibition of cell proliferation, such as CD43 (leukosialin, sialophorin), CD162 (PSGL-1), and CD164 (MGC24v; refs. [26][27][28][29]. Further studies on Porimin should provide more information on the relationship between this membraneassociated mucin and cell death.…”

Costimulation of Host T Lymphocytes by a Trypanosomal trans-Sialidase: Involvement of CD43 Signaling

“…Uninfected littermates were used as controls. CD43 Ϫ/Ϫ and wild-type control mice (17) were a gift from Dr. M. Correa (Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil) and were infected with T. cruzi as above. Cells from infected mice were obtained 21-25 days after infection.…”