Blood Journal
Leading the way in experimental and clinical research in hematology

The cytoplasmic tail of CD45 is released from activated phagocytes and can act as an inhibitory messenger for T cells

  1. Stefanie Kirchberger1,
  2. Otto Majdic1,
  3. Stefan Blüml1,
  4. Catharina Schrauf1,
  5. Judith Leitner1,
  6. Christopher Gerner2,
  7. Wolfgang Paster3,
  8. Nina Gundacker2,
  9. Maria Sibilia2, and
  10. Johannes Stöckl1
  1. 1Institute of Immunology,
  2. 2Institute of Cancer Research, and
  3. 3Department of Molecular Immunology, Medical University of Vienna, Vienna, Austria


CD45 is the prototypic transmembrane protein tyrosine phosphatase (PTP), which is expressed on all nucleated hematopoietic cells and plays a central role in the integration of environmental signals into immune cell responses. Here we report an alternative function for the intracellular domain of CD45. We dis-covered that CD45 is sequentially cleaved by serine/metalloproteinases and γ-secretases during activation of human monocytes and granulocytes by fungal stimuli or phorbol 12-myristate 13-acetate but not by other microbial stimuli. Proteolytic processing of CD45 occurred upon activation of monocytes or granulocytes but not of T cells, B cells, or dendritic cells and resulted in a 95-kDa fragment of the cytoplasmic tail of CD45 (ct-CD45). ct-CD45 was released from monocytes and granulocytes upon activation-induced cell death. Binding studies with ct-CD45 revealed a counter-receptor on preactivated T cells. Moreover, T-cell proliferation induced by dendritic cells or CD3 antibodies was inhibited in the presence of ct-CD45. Taken together, the results of our study demonstrate that fragments of the intracellular domain of CD45 from human phagocytes can function as intercellular regulators of T-cell activation.

  • Submitted February 6, 2008.
  • Accepted May 9, 2008.
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