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Regulatory CD4+CD25+Foxp3+ T Cells Selectively Inhibit the Spontaneous Form of Lymphopenia-Induced Proliferation of Naive T Cells
| Content Provider | Scilit |
|---|---|
| Author | Winstead, Colleen J. Fraser, Joanne M. Khoruts, Alexander |
| Copyright Year | 2008 |
| Description | Regulatory $CD4^{+}CD25^{+}Foxp3^{+}$ T cells play a critical role in controlling autoimmunity and T cell homeostasis. However, their role in regulation of lymphopenia-induced proliferation (LIP), a potential mechanism for generation of autoaggressive T cells, has been poorly defined. Currently, two forms of LIP are recognized: spontaneous and homeostatic. Spontaneous LIP is characterized by fast, burst-like cell-cycle activity, and may allow effector T cell differentiation. Homeostatic LIP is characterized by slow and steady cell cycle activity and is not associated with the acquisition of an effector phenotype. In this study, we demonstrate that $CD4^{+}CD25^{+}Foxp3^{+}$ T cells suppress the spontaneous, but not homeostatic, LIP of naive CD8 and CD4 T cells. However, selective inhibition of spontaneous LIP does not fully explain the tolerogenic role of Tregs in lymphopenia-associated autoimmunity. We show here that suppression of LIP in the lymphoid tissues is independent of Treg-derived IL-10. However, IL-10-deficient Tregs are partially defective in their ability to prevent colitis caused by adoptive transfer of CD4 T cells into $RAG^{−/−}$ mice. We propose that Tregs may inhibit emergence of effector T cells during the inductive phase of the immune response in the secondary lymphoid tissues by IL-10-independent mechanisms. In contrast, Treg-mediated inhibition of established effector T cells does require IL-10. Both Treg functions appear to be important in control of lymphopenia-associated autoimmunity. |
| Ending Page | 7317 |
| Page Count | 13 |
| Starting Page | 7305 |
| ISSN | 00221767 |
| e-ISSN | 15506606 |
| DOI | 10.4049/jimmunol.180.11.7305 |
| Journal | The Journal of Immunology |
| Issue Number | 11 |
| Volume Number | 180 |
| Language | English |
| Publisher | The American Association of Immunologists |
| Publisher Date | 2008-06-01 |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
| Subject | Immunology and Allergy Immunology |
