O papel modulador do gene AIRE - capes

Molecular and Cellular Biochemistry 252: 223–228, 2003.© 2003 Kluwer Academic Publishers. Printed in the Netherlands.223Gene expression profiling during thymus ontogenyand its association with TCRVβ8.1-Dβ2.1rearrangements of inbred mouse strainsAline R. Espanhol, 1,2 Cláudia Macedo, 1 Cristina M. Junta, 1Renato Sousa Cardoso, 1 Geneviève Victorero, 3 Beatrice Loriod, 3Catherine Nguyen, 3 Bertrand Jordan 3 and Geraldo A.S. Passos 1,41Grupo de Imunogenética Molecular, Departamento de Genética, Faculdade de Medicina de Ribeirão Preto, Universidadede São Paulo (USP), Ribeirão Preto; 2 Universidade Federal de São Carlos, Programa de Genética e Evolução, SãoCarlos, SP, Brasil; 3 Unité INSERM Technologies Avancées pour le Génome et la Clinique, Marseille, France; 4 Disciplinade Genética, Faculdade de Odontologia de Ribeirão Preto, USP, Ribeirão Preto, SP, BrasilReceived 13 September 2002; accepted 17 February 2003AbstractThe V(D)J recombination of TCRα and β in early developing T-cells is a highly modulated phenomenon initiated and completedby recombinase complex (RAG-1 and RAG-2), and regulated by other gene products such as interleukins. To furtherevaluate the association of several other gene products with the evolution of TCRVβ8.1 V(D)J rearrangements in vivo, themRNA expression levels of seven interleukins, three cytokines, receptors TCRVβ8.1 and IL-2Rβ, MHC-I/MHC-II, RAG-1/RAG-2 and retroviral superantigen MMTV(SW) were measured by RT-PCR during the fetal development of the thymus ofthree inbred mouse strains (Balb-c, C57Bl/6 and CBA/J). Clustering using the Tree View software, was used to organize thesegenes based on similarity of expression patterns. Each strain displayed a different expression profile during thymus ontogeny.During the late developmental stage the most evident association was the kinetics of MMTV(SW) retrovirus, IL-2Rβ andIL-7 overexpression with reduction of TCRVβ8.1-Dβ2.1 rearrangement in the thymus of CBA/J mice. These data suggest asusceptibility of this strain to expression of MMTV(SW) upon reduction of the rearranged TCRVβ8.1-Dβ2.1 segment in developingthymocytes, with parallel IL-7 overexpression. (Mol Cell Biochem 252: 223–228, 2003)Key words: TCRVβ8.1, V(D)J recombination, gene expression profiling, cytokine, cluster analysis.IntroductionNon-manipulated inbred mouse strains constitute a modelsystem for studies on the effects of different genetic backgroundson the in vivo maturation of thymocytes. In previouswork, we have observed that onset of T-cell receptor(TCRα/β) V(D)J recombination differs among the Balb-c,C57Bl/6 and CBA/J strains [1, 2].The V(D)J recombination in early developing T-cells is ahighly modulated phenomenon. The rearrangements of T-cellreceptor genes (TCRα and β) is initiated and completed bythe recombinase enzymatic complex (RAG-1 and RAG-2),but is regulated by other gene products such as interleukins[3, 4].Stromal cells from the thymus or bone marrow are veryimportant for development of T-cells producing cytokines [5,6]. In this context, interleukin (IL)-7 in particular appears toserve as a proliferative agent before and after gene rearrangementsand possibly as a survival factor during rearrangements[7].Address for offprints: G.A.S. Passos, Grupo de Imunogenética Molecular, Depto. de Genética, Faculdade de Medicina de Ribeirão Preto, SP, Brasil(E-mail: passos@rge.fmrp.usp.br)