Abstract
The membrane receptor 2B4 is a CD2 family member that is involved in lymphocyte activation. A fraction of human CD8+ alphabeta T cells up-regulate 2B4 in vivo, and here we demonstrate that this correlates with the acquisition of effector cell properties such as granzyme B and perforin expression, rapid IFN-gamma production, and down-regulation of the lymph node homing chemokine receptor CCR7. In PBLs from healthy donors, cytomegalovirus-specific effector T cells were 2B4 positive, whereas naive melanoma Ag (Melan-A/melanoma Ag recognized by T cells-1)-specific T cells were 2B4 negative. In melanoma patients, Melan-A-specific T cells up-regulated 2B4 in parallel with in vivo differentiation. This occurred in PBLs after vaccination with Melan-A peptides and in tumor-infiltrated lymph nodes, likely through disease-associated activation of Melan-A-specific T cells. Thus, 2B4 expression correlates with CD8+ T cell differentiation in vivo.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antigens, CD*
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Antigens, Neoplasm
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CD8-Positive T-Lymphocytes / cytology
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CD8-Positive T-Lymphocytes / enzymology
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CD8-Positive T-Lymphocytes / immunology*
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CD8-Positive T-Lymphocytes / metabolism*
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Cancer Vaccines / immunology
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Cancer Vaccines / therapeutic use
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Cell Differentiation / immunology
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Cell Separation
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Epitopes, T-Lymphocyte / analysis
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Granzymes
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Humans
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Interferon-gamma / biosynthesis
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Interphase / immunology
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Lymphocyte Activation
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MART-1 Antigen
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Melanoma / immunology
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Melanoma / therapy
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Membrane Glycoproteins / biosynthesis*
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Neoplasm Proteins / immunology
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Neoplasm Proteins / therapeutic use
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Perforin
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Pore Forming Cytotoxic Proteins
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Receptors, Antigen, T-Cell, alpha-beta / immunology*
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Receptors, Immunologic / biosynthesis*
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Serine Endopeptidases / biosynthesis
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Signaling Lymphocytic Activation Molecule Family
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T-Lymphocyte Subsets / cytology
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T-Lymphocyte Subsets / enzymology
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T-Lymphocyte Subsets / immunology*
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T-Lymphocyte Subsets / metabolism*
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Up-Regulation / immunology
Substances
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Antigens, CD
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Antigens, Neoplasm
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CD244 protein, human
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Cancer Vaccines
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Epitopes, T-Lymphocyte
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MART-1 Antigen
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MLANA protein, human
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Membrane Glycoproteins
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Neoplasm Proteins
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Pore Forming Cytotoxic Proteins
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Receptors, Antigen, T-Cell, alpha-beta
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Receptors, Immunologic
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Signaling Lymphocytic Activation Molecule Family
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Perforin
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Interferon-gamma
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GZMB protein, human
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Granzymes
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Serine Endopeptidases