Submitted February 7, 2008
Accepted May 9, 2008
The cytoplasmic tail of CD45 is released from activated phagocytes and can act as an inhibitory messenger for T cells
Stefanie Kirchberger, Otto Majdic, Stefan Bluml, Catharina Schrauf, Judith Leitner, Christopher Gerner, Wolfgang Paster, Nina Gundacker, Maria Sibilia, and Johannes Stockl*
Institute of Immunology, Medical University of Vienna, Vienna, Austria
Institute of Cancer Research, Medical University of Vienna, Vienna, Austria
Department of Molecular Immunology, Medical University of Vienna, Vienna, Austria
* Corresponding author; email: johannes.stoeckl{at}meduniwien.ac.at.
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 discovered that CD45 is sequentially cleaved by serine/metalloproteinases and 
-secretases during activation of human monocytes and granulocytes by fungal stimuli or PMA 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.
