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IL-10 and TGF-beta induce alloreactive CD4+CD25- T cells to acquire regulatory cell function
Zong-ming Chen1, Matthew J O'Shaughnessy, Irene Gramaglia
1University of Minnesota Cancer Center and Department of Pediatrics, Division of Bone Marrow Transplantation, Minneapolis, MN 55455, USA.
Blood
|March 1, 2003
Summary
Interleukin-10 (IL-10) and transforming growth factor-beta (TGF-beta) induce regulatory CD4+ T cells from CD4+CD25- cells. These cells prevent graft-versus-host disease (GVHD) lethality independently of IL-10 and TGF-beta.
Area of Science:
- Immunology
- Transplantation immunology
Background:
- Interleukin-10 (IL-10) and transforming growth factor-beta (TGF-beta) treatment of mixed lymphocyte reaction (MLR) cultures induce alloantigen-specific hyporesponsiveness.
- This treatment also protects against graft-versus-host disease (GVHD) lethality.
Purpose of the Study:
- To investigate the immunoregulatory function of CD4+ T cells derived from IL-10 and TGF-beta treated MLR cultures.
- To determine the mechanism of action and cellular origin of these regulatory T cells.
Main Methods:
- Primary MLR cultures were treated with IL-10 and TGF-beta.
- The immunoregulatory capacity of recovered CD4+ T cells was assessed in vitro and in vivo.
- Experiments involved CD25 depletion, neutralizing antibodies, and IL-10 deficient T cells.
Main Results:
- CD4+ T cells from treated cultures exhibited significant inhibition of naive alloreactive CD4+ T cell proliferation.
- These tolerized cells reduced GVHD lethality when transferred with naive alloreactive T cells.
- Regulatory capacity was generated from CD4+CD25- T cells and was independent of IL-10 and TGF-beta production.
Conclusions:
- IL-10 and TGF-beta induce CD4+CD25- T cells with potent immunoregulatory function.
- These regulatory T cells prevent GVHD lethality through a mechanism independent of IL-10 and TGF-beta.
- This represents an additional mechanism for preventing GVHD by T cells that escape full tolerance induction.