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A quantitative study of the mechanisms behind thymic atrophy in G alpha i2-deficient mice during colitis development
Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
Systems Biology Research Centre, University of Skövde, Skövde, Sweden.
Örebro University, School of Medicine, Örebro University, Sweden.ORCID iD: 0000-0001-5460-8888
2012 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, no 5, article id e36726Article in journal (Refereed) Published
Abstract [en]

Mice deficient for the G protein subunit G alpha i2 spontaneously develop colitis, a chronic inflammatory disease associated with dysregulated T cell responses. We and others have previously demonstrated a thymic involution in these mice and an aberrant thymocyte dynamics. The G alpha i2(-/-) mice have a dramatically reduced fraction of double positive thymocytes and an increased fraction of single positive (SP) thymocytes. In this study, we quantify a number of critical parameters in order to narrow down the underlying mechanisms that cause the dynamical changes of the thymocyte development in the G alpha i2(-/-) mice. Our data suggest that the increased fraction of SP thymocytes results only from a decreased number of DP thymocytes, since the number of SP thymocytes in the Gai2(-/-) mice is comparable to the control littermates. By measuring the frequency of T cell receptor excision circles (TRECs) in the thymocytes, we demonstrate that the number of cell divisions the G alpha i2(-/-) SP thymocytes undergo is comparable to SP thymocytes from control littermates. In addition, our data show that the mature SP CD4(+) and CD8(+) thymocytes divide to the same extent before they egress from the thymus. By estimating the number of peripheral TREC+ T lymphocytes and their death rate, we could calculate the daily egression of thymocytes. G alpha i2(-/-) mice with no/mild and moderate colitis were found to have a slower export rate in comparison to the control littermates. The quantitative measurements in this study suggest a number of dynamical changes in the thymocyte development during the progression of colitis.

Place, publisher, year, edition, pages
San Francisco, USA: Public Library of Science , 2012. Vol. 7, no 5, article id e36726
National Category
Immunology in the medical area
Research subject
Biomedicine
Identifiers
URN: urn:nbn:se:oru:diva-24419DOI: 10.1371/journal.pone.0036726ISI: 000305336400031PubMedID: 22590596Scopus ID: 2-s2.0-84861002198OAI: oai:DiVA.org:oru-24419DiVA, id: diva2:544541
Funder
Swedish Research CouncilKnowledge Foundation
Note

Funding Agencies:

Swedish Cancer Society 

Foundation of Professor Nanna Svartz

Örebro University 

Swedish Society of Medicine 

Available from: 2012-08-15 Created: 2012-08-15 Last updated: 2018-01-12Bibliographically approved

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Elgbratt, KristinaHultgren-Hörnquist, Elisabeth

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School of Health and Medical Sciences, Örebro University, SwedenSchool of Medicine, Örebro University, Sweden
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