title: Homogeneous expansion of human T-regulatory cells via tumor necrosis factor receptor 2.
abstract: T-regulatory cells (T(regs)) are a rare lymphocyte subtype that shows promise for treating infectious disease, allergy, graft-versus-host disease, autoimmunity, and asthma. Clinical applications of T(regs) have not been fully realized because standard methods of expansion ex vivo produce heterogeneous progeny consisting of mixed populations of CD4 + T cells. Heterogeneous progeny are risky for human clinical trials and face significant regulatory hurdles. With the goal of producing homogeneous T(regs), we developed a novel expansion protocol targeting tumor necrosis factor receptors (TNFR) on T(regs). In in vitro studies, a TNFR2 agonist was found superior to standard methods in proliferating human T(regs) into a phenotypically homogeneous population consisting of 14 cell surface markers. The TNFR2 agonist-expanded T(regs) also were functionally superior in suppressing a key T(reg) target cell, cytotoxic T-lymphocytes. Targeting the TNFR2 receptor during ex vivo expansion is a new means for producing homogeneous and potent human T(regs) for clinical opportunities.
authors.affiliation: Immunobiology Laboratory, Massachusetts General Hospital and Harvard Medical School, Rm 3602, MGH-East, Bldg 149, 13th Street, Boston, MA 02129.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Okubo
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Mera
authors.forename: Limei
authors.initials: L
authors.lastname: Wang
authors.forename: Denise L
authors.initials: DL
authors.lastname: Faustman
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology
chemical_list: D000911:Antibodies, Monoclonal; D016207:Cytokines; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D007376:Interleukin-2; D047889:Receptors, Tumor Necrosis Factor, Type II; D011994:Recombinant Proteins; C415902:TNFRSF1B protein, human; D014409:Tumor Necrosis Factor-alpha