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Converting antigen-specific diabetogenic CD4 and CD8 T cells to TGF-beta producing non-pathogenic regulatory cells following FoxP3 transduction.

Abstract：

:Immuno-regulatory defects, including a reduction in the number and function of regulatory T cells, play an important role in the development of autoimmune diabetes in both humans and non-obese diabetic (NOD) mice. In this study we tested the effect of introduction of FoxP3 into antigen non-specific polyclonal and antigen-specific monoclonal T cells on diabetes development in NOD mice. Transduction of FoxP3 into antigen-specific monoclonal (insulin or BDC2.5 mimotope specific) or antigen non-specific polyclonal T cells using retroviral transduction delayed or prevented diabetes development. However, transduced antigen-specific monoclonal T cells were considerably more effective than polyclonal T cells. Regulatory activity was not limited to CD4 T cells as potent diabetogenic CD8 T cells specific for insulin, were also reduced in pathogenicity by FoxP3 induction. The disease suppressive effect, in both CD4 and CD8 cells, was more evident in spontaneously diabetes-prone NOD hosts (non-lymphopenic) than in lymphopenic NOD.scid hosts. We suggest that this strategy of transducing antigen-specific CD4 or CD8 T cells may be a useful therapeutic approach in the prevention of autoimmune diabetes.

journal_name

J Autoimmun

journal_title

Journal of autoimmunity

authors

Peng J,Dicker B,Du W,Tang F,Nguyen P,Geiger T,Wong FS,Wen L

doi

10.1016/j.jaut.2007.02.015

subject

Has Abstract

pub_date

2007-06-01 00:00:00

pages

188-200

issue

4

eissn

0896-8411

issn

1095-9157

pii

S0896-8411(07)00035-2

journal_volume

28

pub_type

杂志文章

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