Homogeneous Expansion of Human T-Regulatory Cells Via Tumor Necrosis Factor Receptor 2

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...

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Vydané v:	Scientific reports Ročník 3; číslo 1; s. 3153
Hlavní autori:	Okubo, Yoshiaki, Mera, Toshiyuki, Wang, Limei, Faustman, Denise L.
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	London Nature Publishing Group UK 06.11.2013 Nature Publishing Group
Predmet:	13 13/1 631/1647/664/1364 631/61/24 692/308/575 Allergies Animals Antibodies, Monoclonal - immunology Asthma Autoimmune diseases Autoimmunity CD4 antigen CD4-Positive T-Lymphocytes - cytology CD4-Positive T-Lymphocytes - drug effects CD4-Positive T-Lymphocytes - metabolism Cell Proliferation Cell surface Cells, Cultured Clinical trials Cytokines - metabolism Cytotoxicity Forkhead Transcription Factors - metabolism Graft-versus-host reaction Humanities and Social Sciences Humans Immunoregulation Infectious diseases Interleukin-2 - genetics Interleukin-2 - metabolism Interleukin-2 - pharmacology Lymphocytes Lymphocytes T multidisciplinary Necrosis Offspring Receptors, Tumor Necrosis Factor, Type II - agonists Receptors, Tumor Necrosis Factor, Type II - antagonists & inhibitors Receptors, Tumor Necrosis Factor, Type II - metabolism Recombinant Proteins - biosynthesis Recombinant Proteins - genetics Recombinant Proteins - pharmacology Science Surface markers T cell receptors T-Lymphocytes, Regulatory - cytology T-Lymphocytes, Regulatory - drug effects T-Lymphocytes, Regulatory - metabolism Therapeutic applications Tumor necrosis factor Tumor necrosis factor receptor 2 Tumor necrosis factor receptors Tumor Necrosis Factor-alpha - genetics Tumor Necrosis Factor-alpha - metabolism Tumor Necrosis Factor-alpha - pharmacology Tumor necrosis factor-TNF
ISSN:	2045-2322, 2045-2322
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Popis
Shrnutí:	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.
Bibliografia:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	2045-2322 2045-2322
DOI:	10.1038/srep03153