Specific CD45 isoforms differentially regulate T cell receptor signaling.
Multiple isoforms of T cell CD45 tyrosine phosphatase are expressed as a result of alternative RNA splicing among extracellular exons. To discern the presence and identity of distinct functions among CD45 isoforms, we compared thymic T cell activation responses by elevating expression of two CD45 isoforms normally found on quiescent T cells. We report that CD45RABC significantly increased CD4+ thymic T cell proliferation in both a mixed lymphocyte reaction and following anti-T cell receptor (TCR) antibody stimulation. Additionally, CD45RABC enhanced Ca2+ mobilization and phosphotyrosine accumulation, and suppressed the inhibitory effect of anti-CD4 antibodies. By contrast, CD45R0 did not enhance TCR signaling or phosphotyrosine levels in CD4+ thymic T cells and required a TCR co-stimulus to augment cellular proliferation. These studies provide genetic evidence that alternative CD45 isoforms are functionally distinct and disclose a unique mechanism by which T cell immunologic responsiveness can be modified.
Chui
D
D
Biomedical Research Centre, University of British Columbia, Vancouver, Canada.
Ong
C J
CJ
Johnson
P
P
Teh
H S
HS
Marth
J D
JD
D000818:Animals; D000906:Antibodies / Q000276:immunology; D015704:CD4 Antigens / Q000276:immunology; D002118:Calcium / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism*; D008213:Lymphocyte Activation; D051379:Mice; D008822:Mice, Transgenic; D019000:Phosphotyrosine; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D000906:Antibodies; D015704:CD4 Antigens; D007527:Isoenzymes; D011948:Receptors, Antigen, T-Cell; D019000:Phosphotyrosine; D014443:Tyrosine; D017027:Protein Tyrosine Phosphatases; D002118:Calcium