ORCID Profile
0000-0002-9674-0753
Current Organisation
National Institutes of Health
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Publisher: American Society of Hematology
Date: 03-10-2013
DOI: 10.1182/BLOOD-2012-12-472076
Abstract: Ikaros suppresses thymocyte proliferation but induces antiapoptotic molecule expression upon TCR-induced positive selection. Ikaros function is required to prevent clonal expansion and to maintain a random TCR repertoire during thymocyte differentiation.
Publisher: Wiley
Date: 19-03-2020
Publisher: Elsevier BV
Date: 06-2014
Publisher: Elsevier BV
Date: 11-2013
Publisher: The American Association of Immunologists
Date: 15-06-2012
Abstract: All T cells are dependent on IL-7 for their development and for homeostasis. Foxp3+ regulatory T cells (Tregs) are unique among T cells in that they are dependent on IL-2. Whether such IL-2 dependency is distinct from or in addition to an IL-7 requirement has been a confounding issue, particularly because of the absence of an adequate experimental system to address this question. In this study, we present a novel in vivo mouse model where IL-2 expression is intact but IL-7 expression was geographically limited to the thymus. Consequently, IL-7 is not available in peripheral tissues. Such mice were generated by introducing a thymocyte-specific IL-7 transgene onto an IL-7 null background. In these mice, T cell development in the thymus, including Foxp3+ Treg numbers, was completely restored, which correlates with the thymus-specific expression of transgenic IL-7. In peripheral cells, however, IL-7 expression was terminated, which resulted in a general paucity of T cells and a dramatic reduction of Foxp3+ Treg numbers. Loss of Tregs was further accompanied by a significant reduction in Foxp3+ expression levels. These data suggest that peripheral IL-7 is not only necessary for Treg survival but also for upregulating Foxp3 expression. Collectively, we assessed the effect of a selective peripheral IL-7 deficiency in the presence of a fully functional thymus, and we document a critical requirement for in vivo IL-7 in T cell maintenance and specifically in Foxp3+ cell homeostasis.
Publisher: Elsevier BV
Date: 10-2012
Publisher: Wiley
Date: 21-06-2013
No related grants have been discovered for Megan Davis.