Abstract
We previously reported that 4C8 monoclonal antibody (mAb) provides a costimulatory signal to human CD4+ T cells and consequently induces regulatory T (Treg) cells, which are hypo-responsive and suppress the polyclonal response of bystander CD4+ cells in a contact-dependent manner. In this study, we identified the antigen of 4C8 mAb as CD52. Costimulation with Campath-1H, a humanized anti-CD52 mAb, also induced Treg cells. Anti-CD52-induced Treg cells suppressed the proliferation of both CD4+ and CD8+ T cells provided with polyclonal or allogeneic stimulation. When Treg cells were induced from Staphylococcal enterotoxin B (SEB) treated cells, they suppressed the response to SEB more efficiently than that to another superantigen, SEA. Furthermore, anti-CD52-induced Treg cells could be expanded by culture with IL-2 followed by CD52-costimulation, and co-injection of expanded Treg cells suppressed lethal xenogeneic graft versus host disease (GvHD) reactions in SCID mice caused by human peripheral blood mononuclear cells (PBMCs).
MeSH terms
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Alemtuzumab
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Animals
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Antibodies, Monoclonal / immunology
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Antibodies, Monoclonal, Humanized
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Antibodies, Neoplasm / immunology
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Antigens, CD / biosynthesis
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Antigens, CD / immunology*
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Antigens, Neoplasm / immunology*
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CD52 Antigen
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CD8-Positive T-Lymphocytes / cytology
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CD8-Positive T-Lymphocytes / immunology
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Enterotoxins / immunology
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Epitopes, T-Lymphocyte / immunology
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Female
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Forkhead Transcription Factors / biosynthesis
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Forkhead Transcription Factors / genetics
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Forkhead Transcription Factors / immunology
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Glycoproteins / immunology*
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Graft vs Host Disease / immunology
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Humans
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Interleukin-2 / immunology
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Lymphocyte Activation / immunology
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Mice
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Mice, SCID
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Reverse Transcriptase Polymerase Chain Reaction
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T-Lymphocytes, Regulatory / cytology
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T-Lymphocytes, Regulatory / immunology*
Substances
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4C8 antigen, human
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Antibodies, Monoclonal
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Antibodies, Monoclonal, Humanized
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Antibodies, Neoplasm
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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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Enterotoxins
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Epitopes, T-Lymphocyte
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FOXP3 protein, human
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Forkhead Transcription Factors
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Glycoproteins
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Interleukin-2
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enterotoxin B, staphylococcal
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Alemtuzumab