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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| Vydáno v: | Scientific reports Ročník 3; číslo 1; s. 3153 |
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| Hlavní autoři: | , , , |
| Médium: | Journal Article |
| Jazyk: | angličtina |
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London
Nature Publishing Group UK
06.11.2013
Nature Publishing Group |
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| ISSN: | 2045-2322, 2045-2322 |
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| 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. |
|---|---|
| AbstractList | 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. 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. 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.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. T-regulatory cells (Tregs) are a rare lymphocyte subtype that shows promise for treating infectious disease, allergy, graft-versus-host disease, autoimmunity, and asthma. Clinical applications of Tregs 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 Tregs, we developed a novel expansion protocol targeting tumor necrosis factor receptors (TNFR) on Tregs. In in vitro studies, a TNFR2 agonist was found superior to standard methods in proliferating human Tregs into a phenotypically homogeneous population consisting of 14 cell surface markers. The TNFR2 agonist-expanded Tregs also were functionally superior in suppressing a key Treg target cell, cytotoxic T-lymphocytes. Targeting the TNFR2 receptor during ex vivo expansion is a new means for producing homogeneous and potent human Tregs for clinical opportunities. |
| ArticleNumber | 3153 |
| Author | Mera, Toshiyuki Faustman, Denise L. Okubo, Yoshiaki Wang, Limei |
| Author_xml | – sequence: 1 givenname: Yoshiaki surname: Okubo fullname: Okubo, Yoshiaki organization: Immunobiology Laboratory, Massachusetts General Hospital and Harvard Medical School – sequence: 2 givenname: Toshiyuki surname: Mera fullname: Mera, Toshiyuki organization: Immunobiology Laboratory, Massachusetts General Hospital and Harvard Medical School – sequence: 3 givenname: Limei surname: Wang fullname: Wang, Limei organization: Immunobiology Laboratory, Massachusetts General Hospital and Harvard Medical School – sequence: 4 givenname: Denise L. surname: Faustman fullname: Faustman, Denise L. organization: Immunobiology Laboratory, Massachusetts General Hospital and Harvard Medical School |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/24193319$$D View this record in MEDLINE/PubMed |
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| Snippet | T-regulatory cells (T
regs
) are a rare lymphocyte subtype that shows promise for treating infectious disease, allergy, graft-versus-host disease, autoimmunity... T-regulatory cells (T(regs)) are a rare lymphocyte subtype that shows promise for treating infectious disease, allergy, graft-versus-host disease,... T-regulatory cells (Tregs ) are a rare lymphocyte subtype that shows promise for treating infectious disease, allergy, graft-versus-host disease, autoimmunity,... T-regulatory cells (Tregs) are a rare lymphocyte subtype that shows promise for treating infectious disease, allergy, graft-versus-host disease, autoimmunity,... |
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| SubjectTerms | 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 |
| Title | Homogeneous Expansion of Human T-Regulatory Cells Via Tumor Necrosis Factor Receptor 2 |
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