Autoreactive T cells Eescaping thymic deletion in REL-B deficient mice depend on dendritic cell-encoded REL-B for control of autoimmunity

O'Sullivan, B, Pai, S, Street, S, MacDonald, K, Gerondakis, S, Hill, G and Thomas, R (2010). Autoreactive T cells Eescaping thymic deletion in REL-B deficient mice depend on dendritic cell-encoded REL-B for control of autoimmunity. In: Abstract Supplement - 10th Annual Meeting, Federation of Clinical Immunology Societies. 10th Annual Meeting of the Federation-of-Clinical-Immunology-Societies, Boston, MA, U.S.A., (S-134-S-135). 24-27 June 2010. doi:10.1016/j.clim.2010.03.407


Author O'Sullivan, B
Pai, S
Street, S
MacDonald, K
Gerondakis, S
Hill, G
Thomas, R
Title of paper Autoreactive T cells Eescaping thymic deletion in REL-B deficient mice depend on dendritic cell-encoded REL-B for control of autoimmunity
Conference name 10th Annual Meeting of the Federation-of-Clinical-Immunology-Societies
Conference location Boston, MA, U.S.A.
Conference dates 24-27 June 2010
Proceedings title Abstract Supplement - 10th Annual Meeting, Federation of Clinical Immunology Societies   Check publisher's open access policy
Journal name Clinical Immunology   Check publisher's open access policy
Place of Publication Maryland Heights, MO, U.S.A.
Publisher Academic Press
Publication Year 2010
Year available 2010
Sub-type Published abstract
DOI 10.1016/j.clim.2010.03.407
ISSN 1521-6616
Volume 135
Issue Supp. 1
Start page S-134
End page S-135
Total pages 2
Collection year 2011
Language eng
Abstract/Summary In humans and mice, autoimmunity is associated with mutations that attenuate T cell receptor (TCR) signaling capacity, which alter thymic selection, and signaling of the peripheral T cell repertoire. The RelB transcription factor controls maturation of antigen presenting cell function by dendritic cells (DCs). Similar to TCR signaling mutants, RelB-/- mice have severe T cell-dependent autoimmune disease and relative lymphopenia, but normal numbers of FoxP3+ regulatory T cells. By analysis of effector and regulatory T cell phenotype and function, distribution and function of antigen presenting cells (APCs) and DC transfer studies in RelB knockout and RelB-/- bone marrow chimeras, we addressed whether reduced capacity of thymic and peripheral APCs to signal T cells drives autoimmunity in RelB-/-mice. Th2-type RelB-/- CD44hi effector T cells, which escape thymic negative selection due to medullary atrophy and APC deficiency, are susceptible to RelB-/- Treg suppression only when signalled by wild type DCs, with enhanced costimulatory activity. Transfer of RelB-sufficient DCs, to RelB-/- mice reversed peripheral organ inflammatory disease, Th2 cytokine over-production, thymic atrophy and lymphopenia, and rendered effector T cells susceptible to suppression by Treg cells. Thus, similar to defects in TCR signaling, autoimmunity may also result from defects in APC function. In the absence of DC-encoded RelB, progressive T cell and myeloid cell-mediated inflammation, uncontrolled by Treg cells, destroys thymus and other organs. Genetic and environmental factors control the level of RelB expression, and reduced expression is predicted to exacerbate the effect of mutations, such as PTPN22R620W that attenuate TCR signaling capacity. Copyright © 2010 Published by Elsevier Inc.
Q-Index Code CX
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Abstract number S.86.

Document type: Conference Paper
Collections: Non HERDC
UQ Diamantina Institute Publications
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 0 times in Thomson Reuters Web of Science Article
Google Scholar Search Google Scholar
Created: Sun, 29 Aug 2010, 00:07:36 EST