title: Feto-maternal allo-immunity, regulatory T cells and predisposition to auto-immunity. Does it all start in utero?
abstract: During gestation, maternal cells traffic to the fetus leading to the natural phenomenon of microchimerism. Although their persistence in offspring has been associated with several autoimmune disorders, the precise role of maternal cells in these disorders remains unclear. We aimed to evaluate whether alloreactive maternal T cells could directly trigger a graft-vs.-host like reaction or indirectly influence the development of the offspring's regulatory T cells (Treg) favoring autoimmunity. In a specific breeding strategy, we recently reported that maternal allogeneic T cells changed fetal Treg development and their quantities in mesenteric lymph nodes, leading to early signs of inflammation in the gut later in life. Although maternal microchimeric T cells were found in newborn tissues, we could not detect any cells in the gut from adult offspring where the inflammation occurred. Thus, strongly alloreactive maternal microchimeric T cells may indirectly drive the offspring to gut inflammation. We believe these results suggest a new mechanism for predisposition to auto-immunity.
authors.affiliation: QIMR Berghofer Medical Research Institute; Brisbane, QLD Australia.
authors.forename: Lucie
authors.initials: L
authors.lastname: Leveque
authors.affiliation: The University of Queensland; UQ Centre for Clinical Research; Experimental Dermatology Group; Brisbane, QLD Australia.
authors.forename: Kiarash
authors.initials: K
authors.lastname: Khosrotehrani
mesh_terms: D015551:Autoimmunity / Q000235:genetics*; D046528:Chimerism; D005260:Female; D006801:Humans; D008297:Male; D008431:Maternal-Fetal Exchange; D018448:Models, Immunological; D011247:Pregnancy; D050378:T-Lymphocytes, Regulatory
keywords: autoimmunity; maternal microchimerism; pregnancy; regulatory T cells; self-antigens
references.citation: Arthritis Rheum. 2004 Mar;50(3):906-14
references.pmid: 15022334
references.citation: Blood. 2002 Mar 1;99(5):1572-7
references.pmid: 11861270
references.citation: Curr Opin Organ Transplant. 2009 Aug;14(4):439-47
references.pmid: 19512930
references.citation: J Autoimmun. 2011 May;36(3-4):253-62
references.pmid: 21414756
references.citation: J Autoimmun. 2014 May;50:51-8
references.pmid: 24268809
references.citation: J Immunol. 2004 Apr 15;172(8):5041-6
references.pmid: 15067086
references.citation: N Engl J Med. 1998 Dec 3;339(23):1657-64
references.pmid: 9834302
references.citation: Blood. 2006 Jan 1;107(1):404-9
references.pmid: 16150938
references.citation: Am J Obstet Gynecol. 2010 May;202(5):476.e1-9
references.pmid: 20452494
references.citation: Autoimmun Rev. 2003 May;2(3):133-9
references.pmid: 12848954
references.citation: Chimerism. 2011 Jul;2(3):71-7
references.pmid: 22163064
references.citation: J Immunol. 2007 Nov 15;179(10):6749-61
references.pmid: 17982065
references.citation: Lancet. 2000 Dec 23-30;356(9248):2156-7
references.pmid: 11191546
references.citation: Science. 2008 Dec 5;322(5907):1562-5
references.pmid: 19056990
references.citation: Proc Natl Acad Sci U S A. 2007 Jan 30;104(5):1637-42
references.pmid: 17244711