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Generation of Induced Regulatory T Cells from Primary Human Naïve and Memory T Cells
Published on: April 16, 2012
Control of T-cell activation by CD4+ CD25+ suppressor T cells.
E M Shevach1, R S McHugh, C A Piccirillo
1Cellular Immunology Section, Laboratory of Immunology, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. ems1@mail.nih.gov
Immunological Reviews
|November 28, 2001
Summary
Depleting CD4+ T cells expressing CD25 (interleukin-2 receptor alpha-chain) causes organ-specific autoimmunity. Restoring these CD4+ CD25+ cells prevents disease, highlighting their crucial role in immune regulation and preventing autoimmune conditions.
Area of Science:
- Immunology
- Autoimmunity
- Cellular Immunology
Background:
- CD4+ T cells expressing CD25 (interleukin-2 receptor alpha-chain) are a minor subpopulation crucial for immune homeostasis.
- Depletion of these cells leads to the development of organ-specific autoimmune diseases.
- Understanding the function of CD4+ CD25+ T cells is vital for autoimmune disease research.
Purpose of the Study:
- To investigate the role of CD4+ CD25+ T cells in preventing organ-specific autoimmunity.
- To elucidate the mechanisms by which CD4+ CD25+ T cells exert their suppressive functions.
- To explore the potential of CD4+ CD25+ T cells in therapeutic interventions for autoimmune diseases.
Main Methods:
- Neonatal thymectomy and adult CD4+ T cell depletion using anti-CD25 and complement to study autoimmunity.
- Reconstitution experiments with CD4+ CD25+ cells to assess disease prevention.
- In vitro co-culture assays to analyze T cell suppression mediated by CD4+ CD25+ cells.
- Transgenic mouse models expressing T-cell receptors recognizing specific autoantigens.
Main Results:
- Depletion of CD4+ CD25+ T cells induced organ-specific autoimmunity, which was preventable by cell reconstitution.
- Suppression of autoimmune gastritis by CD4+ CD25+ T cells was independent of IL-4, IL-10, and TGF-beta.
- Mice with transgenic T-cell receptors for H/K ATPase developed early-onset autoimmune gastritis.
- CD4+ CD25+ T cells demonstrated potent, cytokine-independent, cell contact-dependent suppression of CD4+ and CD8+ T cell activation in vitro.
- Suppressor effector function activation was independent of CD28/CTLA-4 co-stimulation.
Conclusions:
- CD4+ CD25+ T cells are essential for preventing organ-specific autoimmunity.
- These cells function as potent suppressors of autoreactive T cells through direct cell-cell interactions.
- Activation of CD4+ CD25+ T cells via their TCR leads to the generation of suppressor effector cells.
- The findings support a model where CD4+ CD25+ T cells recognize autoantigens and suppress autoreactive T cells at sites of inflammation.
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