title: A quantitative study of the mechanisms behind thymic atrophy in Gαi2-deficient mice during colitis development.
abstract: Mice deficient for the G protein subunit Gαi2 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 Gαi2(-/-) 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 Gαi2(-/-) 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 Gαi2(-/-) 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 Gαi2(-/-) 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. Gαi2(-/-) 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.
authors.affiliation: School of Health and Medical Sciences, Örebro University, Örebro, Sweden.
authors.forename: Kristina
authors.initials: K
authors.lastname: Elgbratt
authors.forename: Andreas
authors.initials: A
authors.lastname: Jansson
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Hultgren-Hörnquist
mesh_terms: D000818:Animals; D001284:Atrophy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015704:CD4 Antigens / Q000378:metabolism; D016827:CD8 Antigens / Q000378:metabolism; D003092:Colitis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051960:GTP-Binding Protein alpha Subunit, Gi2; D051379:Mice; D018345:Mice, Knockout; D060168:Thymocytes / Q000378:metabolism* / Q000473:pathology; D013950:Thymus Gland / Q000378:metabolism* / Q000473:pathology
chemical_list: D015704:CD4 Antigens; D016827:CD8 Antigens; D051960:GTP-Binding Protein alpha Subunit, Gi2; C498016:Gnai2 protein, mouse