Targeted disruption of CD43 gene enhances T lymphocyte adhesion.
CD43 is a major leukocyte surface glycoprotein thought to have important functions for T lymphocyte adhesion and activation. We investigated the function of CD43 by using gene targeting to eliminate CD43 expression in the human T lymphocyte line CEM and then testing their adhesive phenotype. Loss of CD43 expression by the CEM cells enhanced their homotypic adhesion and binding to two distinct ligands, fibronectin and HIV-1 gp120. The enhanced homotypic adhesion was blocked specifically by an anti-beta 1 integrin mAb, and the enhanced binding to fibronectin and gp120 was blocked specifically by anti-beta 1 integrin and anti-CD4 mAb, respectively. Partial reconstitution of CD43 expression in the CD43-negative cells resulted in a corresponding reversion to a less adhesive phenotype. These data suggest that CD43 interferes with T lymphocyte adhesion and that CD43 can regulate lymphocyte adhesion by providing a threshold that must be overcome for cell-cell and cell-ligand interactions to occur.
Manjunath
N
N
Department of Medicine, New England Medical Center Hospitals, Boston, Massachusetts 02111.
Johnson
R S
RS
Staunton
D E
DE
Pasqualini
R
R
Ardman
B
B
D015703:Antigens, CD; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000502:physiology*; D005353:Fibronectins / Q000378:metabolism; D005796:Genes; D015699:HIV Envelope Protein gp120 / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D051917:Leukosialin; D008024:Ligands; D016254:Mutagenesis, Insertional; D012795:Sialoglycoproteins / Q000502:physiology*; D013601:T-Lymphocytes / Q000166:cytology*
D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D005353:Fibronectins; D015699:HIV Envelope Protein gp120; D051917:Leukosialin; D008024:Ligands; C465014:SPN protein, human; D012795:Sialoglycoproteins