title: Genetic control of HgCl2-induced IgE and autoimmunity by a 117-kb interval on rat chromosome 9 through CD4 CD45RChigh T cells.
abstract: Gold or mercury salts trigger a dramatic IgE response and a CD4 T-cell-dependent nephropathy in Brown-Norway (BN), but not in Lewis (LEW) rats. We previously identified the 1.1-Mb Iresp3 (immunoglobin response QTL3) locus on chromosome 9 that controls these gold salt-triggered immune disorders. In the present work, we investigated the genetic control of HgCl(2)-induced immunological disorders and assessed the relative contribution of the CD45RC(high) and CD45RC(low) CD4 T-cell subpopulations in this control. By using interval-specific congenic lines, we narrowed down Iresp3 locus to 117-kb and showed that BN rats congenic for the LEW 117-kb were protected from HgCl(2)-triggered IgE response and nephropathy. This 117-kb interval also controls CD45RC expression by CD4 T cells and the ability of CD45RC(high) CD4 T cells to trigger the autoimmune disorders resulting from HgCl(2) administration. This 117-kb region contains four genes, including Vav1, a strong candidate gene according to its cellular function and exclusive expression in hematopoietic cells. Thus, this study highlights the role of the CD45RC(high) CD4 T-cell subpopulation in the opposite susceptibility of BN and LEW rats to HgCl(2)-triggered immune disorders and identifies a 117-kb interval on chromosome 9 that has a key role in their functions.
authors.affiliation: UMR Inserm, U1043, Toulouse, France.
authors.forename: C
authors.initials: C
authors.lastname: Pedros
authors.forename: O
authors.initials: O
authors.lastname: Papapietro
authors.forename: C
authors.initials: C
authors.lastname: Colacios
authors.forename: A
authors.initials: A
authors.lastname: Casemayou
authors.forename: I
authors.initials: I
authors.lastname: Bernard
authors.forename: V
authors.initials: V
authors.lastname: Garcia
authors.forename: D
authors.initials: D
authors.lastname: Lagrange
authors.forename: B
authors.initials: B
authors.lastname: Mariamé
authors.forename: O
authors.initials: O
authors.lastname: Andreoletti
authors.forename: G J
authors.initials: GJ
authors.lastname: Fournié
authors.forename: A
authors.initials: A
authors.lastname: Saoudi
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000139:chemically induced / Q000235:genetics / Q000276:immunology; D015551:Autoimmunity / Q000235:genetics*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D033481:Chromosomes, Mammalian / Q000235:genetics; D056426:Genetic Loci; D007073:Immunoglobulin E / Q000235:genetics*; D017493:Leukocyte Common Antigens / Q000235:genetics / Q000378:metabolism; D008627:Mercuric Chloride / Q000633:toxicity; D009393:Nephritis / Q000139:chemically induced / Q000235:genetics / Q000276:immunology; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew
chemical_list: D007073:Immunoglobulin E; D008627:Mercuric Chloride; D017493:Leukocyte Common Antigens