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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Bibliographic Details
Published in:Scientific reports Vol. 3; no. 1; p. 3153
Main Authors: Okubo, Yoshiaki, Mera, Toshiyuki, Wang, Limei, Faustman, Denise L.
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 06.11.2013
Nature Publishing Group
Subjects:
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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
Online Access:Get full text
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Summary: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.
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ISSN:2045-2322
2045-2322
DOI:10.1038/srep03153