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CD45 ligation induces programmed cell death in T and B lymphocytes
S J Klaus1, S P Sidorenko, E A Clark
1Department of Immunology, Regional Primate Research Center, University of Washington, Seattle 98195, USA.
Journal of Immunology (Baltimore, Md. : 1950)
|April 15, 1996
Summary
CD45 protein tyrosine phosphatase ligation triggers T cell apoptosis, a novel finding in lymphocyte regulation. This cell death pathway, distinct from Fas-mediated apoptosis, involves cytoskeletal linkage and is modulated by co-ligation with other receptors.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- CD45 protein tyrosine phosphatase is crucial for regulating antigen receptor signaling in lymphocytes.
- Co-ligation of CD45 with antigen receptors can inhibit signaling, impacting T cell IL-2 production and proliferation.
Purpose of the Study:
- To investigate the role of CD45 ligation in lymphocyte cell death.
- To characterize the mechanism and morphological features of CD45-induced apoptosis.
- To explore the relationship between CD45, CD3, CD95, and lymphocyte apoptosis.
Main Methods:
- Induction of apoptosis in normal T cells and B cells using CD45 monoclonal antibodies (mAbs).
- Assessment of cell death using inhibitors of protein tyrosine kinases, phosphatases, RNA/protein synthesis, and cyclosporin A.
- Morphological analysis of apoptosis, including nuclear condensation and membrane blebbing.
- Investigation of CD45 and CD95 co-ligation effects on cell death.
- Analysis of CD45 association with detergent-insoluble cell fractions.
Main Results:
- CD45 ligation alone induces apoptosis in normal T cells, potentiated by CD3 cross-linking.
- CD45-induced cell death occurs in normal B cells and T/B cell lines.
- Inhibitors of protein tyrosine kinases and phosphatases block CD45-induced apoptosis, but not RNA/protein synthesis inhibitors or cyclosporin A.
- Morphologically, CD45-mediated apoptosis resembles CD95 (Fas)-induced death but lacks DNA fragmentation.
- Co-ligation of CD45 and CD95 modulates CD45-induced cell death.
- CD45 cross-linking leads to its association with the detergent-insoluble cell fraction.
Conclusions:
- CD45 plays a novel role in regulating lymphocyte apoptosis in addition to its known role in proliferation.
- CD45-induced apoptosis involves cytoskeletal linkage and distinct molecular pathways compared to Fas-mediated apoptosis.
- Understanding CD45's role in lymphocyte death provides new insights into immune regulation.