The cytoplasmic tail of CD45 is released from activated phagocytes and can act as an inhibitory messenger for T cells.
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 gamma-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.
Institute of Immunology, Medical University of Vienna, Vienna, Austria.
Stefanie
S
Kirchberger
Otto
O
Majdic
Stefan
S
Blüml
Catharina
C
Schrauf
Judith
J
Leitner
Christopher
C
Gerner
Wolfgang
W
Paster
Nina
N
Gundacker
Maria
M
Sibilia
Johannes
J
Stöckl
D049109:Cell Proliferation; D002478:Cells, Cultured; D006098:Granulocytes; D006801:Humans; D017493:Leukocyte Common Antigens / Q000378:metabolism*; D008213:Lymphocyte Activation; D045726:Metalloproteases / Q000378:metabolism; D009000:Monocytes; D010446:Peptide Fragments / Q000502:physiology*; D010586:Phagocytes / Q000737:chemistry / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology*
D010446:Peptide Fragments; D017493:Leukocyte Common Antigens; D045726:Metalloproteases