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A Quantitative Study of the Mechanisms behind Thymic Atrophy in G alpha i2-Deficient Mice during Colitis Development
Univ Örebro, Sch Hlth & Med Sci, Orebro, Sweden.
University of Skövde, School of Life Sciences. University of Skövde, The Systems Biology Research Centre.ORCID iD: 0000-0003-3747-5950
Univ Örebro, Sch Hlth & Med Sci, Orebro, Sweden.
2012 (English)In: PLOS ONE, E-ISSN 1932-6203, Vol. 7, no 5, p. e36726-Article 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
2012. Vol. 7, no 5, p. e36726-
National Category
Immunology in the medical area
Research subject
Natural sciences
Identifiers
URN: urn:nbn:se:his:diva-6192DOI: 10.1371/journal.pone.0036726ISI: 000305336400031PubMedID: 22590596Scopus ID: 2-s2.0-84861002198OAI: oai:DiVA.org:his-6192DiVA, id: diva2:543546
Available from: 2012-08-08 Created: 2012-08-08 Last updated: 2021-08-31Bibliographically approved

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Jansson, Andreas

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