Abstract
T-cell regulation by CD52-expressing CD4 T cells appears to operate by two different and possibly synergistic mechanisms. The first is by its release from the cell surface of CD4 T cells that express high levels of CD52 that then binds to the inhibitory sialic acid-binding immunoglobulin-like lectins-10 (Siglec-10) receptor to attenuate effector T-cell activation by impairing phosphorylation of T-cell receptor associated lck and zap-70. The second mechanism appears to be by crosslinkage of the CD52 molecules by an as yet unidentified endogenous ligand that is mimicked by a bivalent anti-CD52 antibody that results in their expansion.
MeSH terms
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Animals
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Antibodies / pharmacology
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Antigens, CD / genetics
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Antigens, CD / immunology*
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Antigens, Neoplasm / genetics
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Antigens, Neoplasm / immunology*
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CD4-Positive T-Lymphocytes / cytology
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CD4-Positive T-Lymphocytes / immunology*
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CD4-Positive T-Lymphocytes / metabolism
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CD52 Antigen
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Cell Proliferation / drug effects
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Cytokines / genetics
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Cytokines / immunology
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Gene Expression Regulation / immunology*
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Glycoproteins / agonists
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Glycoproteins / genetics
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Glycoproteins / immunology*
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Humans
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Lectins / genetics
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Lectins / immunology
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Lymphocyte Activation / drug effects
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Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / genetics
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Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / immunology
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Mice
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Receptors, Antigen, T-Cell / agonists
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Receptors, Antigen, T-Cell / genetics
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Receptors, Antigen, T-Cell / immunology*
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Receptors, Cell Surface / genetics
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Receptors, Cell Surface / immunology
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Signal Transduction
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T-Lymphocytes, Regulatory / cytology
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T-Lymphocytes, Regulatory / immunology*
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T-Lymphocytes, Regulatory / metabolism
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ZAP-70 Protein-Tyrosine Kinase / genetics
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ZAP-70 Protein-Tyrosine Kinase / immunology
Substances
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Antibodies
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Antigens, CD
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Antigens, Neoplasm
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CD52 Antigen
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CD52 protein, human
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Cytokines
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Glycoproteins
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Lectins
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Receptors, Antigen, T-Cell
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Receptors, Cell Surface
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SIGLEC10 protein, human
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Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
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ZAP-70 Protein-Tyrosine Kinase