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PMID: 12106494 Published · ppublish English Editorial Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Review

The potential of human regulatory T cells generated ex vivo as a treatment for lupus and other chronic inflammatory diseases.

Arthritis research ·Vol. 4 ·No. 4 ·2002-00-00 ·Pages 241-6

Horwitz DA, Gray JD, Zheng SG

Abstract

Regulatory T cells prevent autoimmunity by suppressing the reactivity of potentially aggressive self-reactive T cells. Contact-dependent CD4+ CD25+ 'professional' suppressor cells and other cytokine-producing CD4+ and CD8+ T-cell subsets mediate this protective function. Evidence will be reviewed that T cells primed with transforming growth factor (TGF)-beta expand rapidly following restimulation. Certain CD4+ T cells become contact-dependent suppressor cells and other CD4+ and CD8+ cells become cytokine-producing regulatory cells. This effect is dependent upon a sufficient amount of IL-2 in the microenvironment to overcome the suppressive effects of TGF-beta. The adoptive transfer of these suppressor cells generated ex vivo can protect mice from developing chronic graft-versus-host disease with a lupus-like syndrome and alter the course of established disease. These data suggest that autologous T cells primed and expanded with TGF-beta have the potential to be used as a therapy for patients with systemic lupus erythematosus and other chronic inflammatory diseases. This novel adoptive immunotherapy also has the potential to prevent the rejection of allogeneic transplants.

MeSH Terms
Animals CD4-Positive T-Lymphocytes/cytology,immunology Cell Transplantation Humans Immunotherapy Interleukin-2/immunology Lupus Erythematosus, Systemic/immunology,therapy Lymphocyte Activation Receptors, Interleukin-2/immunology T-Lymphocyte Subsets/cytology,immunology T-Lymphocytes, Regulatory/cytology,immunology Transforming Growth Factor beta/immunology
Chemicals
Interleukin-2 Receptors, Interleukin-2 Transforming Growth Factor beta
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Horwitz David A
The Division of Rheumatology and Immunology, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA. dhorwitz@hsc.usc.edu
Gray J Dixon
Zheng Song Guo
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Article Info
Journal
Arthritis research
Abbr.
Arthritis Res
ISSN
1465-9905
DOI
10.1186/ar414
Email
dhorwitz@hsc.usc.edu
Published
2002-00-00
Epub
2002-00-12
Pages
241-6
Language
English
Region
England
NLM ID
100913255
PMCID
PMC128930
Subset
IM
Grants
NIAID NIH HHS · R01 AI041768 · United States
NIAID NIH HHS · AI 41786 · United States
External Links
PubMed source DOI: 10.1186/ar414 PMC Full Text
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