title: An anti-CD45RO/RB monoclonal antibody modulates T cell responses via induction of apoptosis and generation of regulatory T cells.
abstract: The effects of a chimeric monoclonal antibody (chA6 mAb) that recognizes both the RO and RB isoforms of the transmembrane protein tyrosine phosphatase CD45 on human T cells were investigated. Chimeric A6 (chA6) mAb potently inhibited antigen-specific and polyclonal T cell responses. ChA6 mAb induced activation-independent apoptosis in CD4(+)CD45RO/RB(high) T cells but not in CD8(+) T cells. In addition, CD4(+) T cell lines specific for tetanus toxoid (TT) generated in the presence of chA6 mAb were anergic and suppressed the proliferation and interferon (IFN)-gamma production by TT-specific effector T cells by an interleukin-10-dependent mechanism, indicating that these cells were equivalent to type 1 regulatory T cells. Similarly, CD8(+) T cell lines specific for the influenza A matrix protein-derived peptide (MP.58-66) generated in the presence of chA6 mAb were anergic and suppressed IFN-gamma production by MP.58-66-specific effector CD8(+) T cells. Furthermore, chA6 mAb significantly prolonged human pancreatic islet allograft survival in nonobese diabetic/severe combined immunodeficiency mice injected with human peripheral blood lymphocytes (hu-PBL-NOD/SCID). Together, these results demonstrate that the chA6 mAb is a new immunomodulatory agent with multiple modes of action, including deletion of preexisting memory and recently activated T cells and induction of anergic CD4(+) and CD8(+) regulatory T cells.
authors.affiliation: San Raffaele Telethon Institute for Gene Therapy, 20132 Milan, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Gregori
authors.forename: Patrizia
authors.initials: P
authors.lastname: Mangia
authors.forename: Rosa
authors.initials: R
authors.lastname: Bacchetta
authors.forename: Eleonora
authors.initials: E
authors.lastname: Tresoldi
authors.forename: Frank
authors.initials: F
authors.lastname: Kolbinger
authors.forename: Catia
authors.initials: C
authors.lastname: Traversari
authors.forename: Josè M
authors.initials: JM
authors.lastname: Carballido
authors.forename: Jan E
authors.initials: JE
authors.lastname: de Vries
authors.forename: Ulf
authors.initials: U
authors.lastname: Korthäuer
authors.forename: Maria-Grazia
authors.initials: MG
authors.lastname: Roncarolo
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D017209:Apoptosis; D017252:CD3 Complex; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D006085:Graft Survival; D006801:Humans; D016381:Islets of Langerhans Transplantation / Q000276:immunology; D017493:Leukocyte Common Antigens / Q000276:immunology*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008840:Microfilament Proteins; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D011505:Protein-Tyrosine Kinases; D013745:Tetanus Toxoid / Q000494:pharmacology
chemical_list: D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D008840:Microfilament Proteins; C485188:TWF1 protein, human; D013745:Tetanus Toxoid; D011505:Protein-Tyrosine Kinases; D017493:Leukocyte Common Antigens; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1