Abstract
Both thymic and extrathymic T lineage development are characterized by cytokine-dependent regulation of complex proliferative, differentiative, and anti-apoptotic processes. The role of the γc-dependent cytokines in this program has been interpreted as limited to the activity of IL-7. However, through the analysis of double knock-out mice, which lack signaling through the IL-7R and other γc-dependent cytokines, we revealed a role for IL-15 in the production of early thymic pro-T cells. Although IL-2 does not function in the production of thymocytes, thymic restoration of IL-2R expression prevented fatal autoimmunity associated with IL-2- or IL-2R-deficient mice, suggesting that IL-2R functions non-redundantly at the level of the thymus to regulate self-reactivity. Moreover, IL-2, IL-7, and IL-15 also extend their developmental effects beyond the thymus to other sites of T lymphocyte production, including the gut. Here, their redundant and non-redundant activities are directly correlated to the development of phenotypically diverse subsets of intestinal intraepithelial lymphocytes. (C) 2000 Academic Press.
Original language | English (US) |
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Pages (from-to) | 465-474 |
Number of pages | 10 |
Journal | Seminars in Immunology |
Volume | 12 |
Issue number | 5 |
DOIs | |
State | Published - Jan 1 2000 |
Keywords
- Development
- IL-15
- IL-2
- IL-7
- T cell
ASJC Scopus subject areas
- Immunology and Allergy
- Infectious Diseases
- Immunology