Regulatory T cells generated ex vivo as an approach for the therapy of autoimmune disease
| Autor: | Satoshi Yamagiwa, Ju Hua Wang, David A. Horwitz, Song Guo Zheng, J. Dixon Gray, Kazuo Ohtsuka |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
CD4-Positive T-Lymphocytes
Graft Rejection T-Lymphocytes Immunology Graft vs Host Disease Cell Communication CD8-Positive T-Lymphocytes Autoimmune Diseases Interleukin 21 Transforming Growth Factor beta Animals Humans Immunology and Allergy Cytotoxic T cell IL-2 receptor Antigen-presenting cell CD40 biology ZAP70 Models Immunological Cell Differentiation Receptors Interleukin-2 Natural killer T cell Adoptive Transfer Interleukin-10 Cell biology Interleukin 12 biology.protein Interleukin-2 Mitogens Cell Division |
| Zdroj: | Seminars in Immunology. 16:135-143 |
| ISSN: | 1044-5323 |
| DOI: | 10.1016/j.smim.2003.12.009 |
| Popis: | Regulatory T cells control the reactivity of potentially harmful, self-reactive T cells and prevent autoimmune diseases. Significant progress has been made in the identification, derivation, and mechanism of action of T regulatory cells, previously called suppressor T cells. Heterogeneous T regulatory subsets can be grouped into naturally occurring and those induced in the periphery. Here, we consider whether we can harness T regulatory cells to function as a therapeutic agent for patients with established autoimmune diseases. Since the principal function of thymus-derived, natural CD4+CD25+ cells is to prevent autoimmunity, this subset would be an obvious choice. Besides their contact-dependent, cytokine-independent mechanism of action, they can also induce other CD4+ cells to become suppressor cells. However, only few natural CD4+CD25+ cells circulate in human peripheral blood. Alternatively, one can use IL-2 and TGF-beta to generate large numbers of CD4+CD25+ regulatory T cells ex vivo from naive T cells. These cells have the phenotypic and functional properties similar to natural CD4+CD25+ cells, including the capacity to induce CD4+CD25- cells to develop suppressive activity. These natural-like CD4+CD25+ regulatory T cells are the product of separate effects of IL-2 and TGF-beta on both natural CD4+CD25+ and CD4+CD25- cells. The ability of natural-like CD4+CD25+ cells to induce other CD4+CD25- cells to develop suppressive activity is both contact-dependent and cytokine-dependent. Thus, the effects of IL-2 and TGF-beta on both natural CD4+CD25+ cells and CD4+CD25- cells may trigger a continuous loop which results in the renewal of antigen-specific CD4+ regulatory T cells. These studies suggest that the adoptive transfer of CD4+ T regulatory cells generated ex vivo with IL-2 and TGF-beta as a treatment for autoimmune diseases may have sustained, long-term beneficial effects. |
| Databáze: | OpenAIRE |
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