NDLI: Preferential control of induced regulatory T cell homeostasis via a Bim/Bcl-2 axis.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Wang, X. Szymczak-Workman, A. L. Gravano, D. M. Workman, C. J. Green, D. R. Vignali, D. A. A.
Description	Country affiliation: United States Author Affiliation: Wang X ( Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.)
Abstract	Apoptosis has an essential role in controlling T cell homeostasis, especially during the contraction phase of an immune response. However, its contribution to the balance between effector and regulatory populations remains unclear. We found that Rag1(-/-) hosts repopulated with Bim(-/-) conventional CD4(+) T cells (Tconv) resulted in a larger induced regulatory T cell (iTreg) population than mice given wild-type (WT) Tconv. This appears to be due to an increased survival advantage of iTregs compared with activated Tconv in the absence of Bim. Downregulation of Bcl-2 expression and upregulation of Bim expression were more dramatic in WT iTregs than activated Tconv in the absence of IL-2 in vitro. The iTregs generated following Tconv reconstitution of Rag1(-/-) hosts exhibited lower Bcl-2 expression and higher Bim/Bcl-2 ratio than Tconv, which indicates that iTregs were in an apoptosis-prone state in vivo. A significant proportion of the peripheral iTreg pool exhibits low Bcl-2 expression indicating increased sensitivity to apoptosis, which may be a general characteristic of certain Treg subpopulations. In summary, our data suggest that iTregs and Tconv differ in their sensitivity to apoptotic stimuli due to their altered ratio of Bim/Bcl-2 expression. Modulating the apoptosis pathway may provide novel therapeutic approaches to alter the balance between effector T cells and Tregs.
File Format	HTM / HTML
e-ISSN	20414889
DOI	10.1038/cddis.2012.9
Journal	Cell Death and Disease
Volume Number	3
Language	English
Publisher	Nature Publishing Group
Publisher Date	2012-02-09
Publisher Place	Great Britain (UK)
Access Restriction	Open
Subject Keyword	Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't Interleukin-2 Antigens, Cd4 Cytology Homeostasis Adoptive Transfer Immunology Genetics Spleen Intestines Signal Transduction Inflammatory Bowel Diseases Lymphocyte Activation Proto-oncogene Proteins Deficiency Mice, Inbred C57bl Gene Expression Regulation T-lymphocytes, Regulatory Enzyme-linked Immunosorbent Assay Mice, Knockout Membrane Proteins Discipline Cell Biology Pathology Apoptosis Regulatory Proteins Animals Homeodomain Proteins Mice Proto-oncogene Proteins C-bcl-2 Forkhead Transcription Factors Apoptosis
Content Type	Text
Resource Type	Article

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