CD8+ T-cell clones deficient in the expression of the CD45 protein tyrosine phosphatase have impaired responses to T-cell receptor stimuli.
CD45 is a high-molecular-weight transmembrane protein tyrosine phosphatase expressed only by nucleated cells of hematopoietic origin. To examine function, mouse CD8+ cytolytic T-cell clones were derived that had a specific defect in the expression of CD45. Northern (RNA) blot analysis indicates that the CD45 deficiency is due to either a transcriptional defect or mRNA instability. The CD45-deficient cells were greatly diminished in their ability to respond to antigen. All functional parameters of T-cell receptor signalling analyzed (cytolysis of targets, proliferation, and cytokine production) were markedly diminished. A CD45+ revertant was isolated, and the ability to respond to antigen was restored. These results support a central and immediate role for this transmembrane protein tyrosine phosphatase in T-cell receptor signalling.
Weaver
C T
CT
Department of Pathology, Washington University School of Medicine, St. Louis, Missouri 6311.
Pingel
J T
JT
Nelson
J O
JO
Thomas
M L
ML
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis* / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte; D015152:Blotting, Northern; D016827:CD8 Antigens; D002455:Cell Division; D002460:Cell Line; D002999:Clone Cells; D005260:Female; D005434:Flow Cytometry; D006649:Histocompatibility Antigens / Q000096:biosynthesis* / Q000378:metabolism; D017493:Leukocyte Common Antigens; D008222:Lymphokines / Q000378:metabolism; D051379:Mice; D008808:Mice, Inbred CBA; D008811:Mice, Inbred DBA; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D017027:Protein Tyrosine Phosphatases; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D015398:Signal Transduction; D013602:T-Lymphocytes, Cytotoxic / Q000201:enzymology* / Q000276:immunology / Q000378:metabolism
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D016827:CD8 Antigens; D006649:Histocompatibility Antigens; D008222:Lymphokines; D011948:Receptors, Antigen, T-Cell; D010749:Phosphoprotein Phosphatases; D017493:Leukocyte Common Antigens; D017027:Protein Tyrosine Phosphatases