O papel modulador do gene AIRE - capes

1048 D.A.R. Magalhães et al. / Molecular Immunology 42 (2005) 1043–1048cells, we have found statistically significant expression ofgenes whose functions are associated with thymocytes.The genes selected for discussion in this study may havea broader functions(s) during thymus development in celltypes other than thymocytes. However, these aspects are stillan open matter.Taken together, our findings demonstrate that the cDNAmicroarrays and the bioinformatics programs employed herewere useful tools to demonstrate the changes in the geneexpression pattern of developing thymus which may reflectspecific organ transcriptome programs.AcknowledgementsThis research was supported by the Brazilian agenciesFundação de Amparo à Pesquisa do Estado de São Paulo(Fapesp, 99/12135-9, 01/08278-0) and Conselho Nacionalde Desenvolvimento Científico e Tecnológico (CNPq). Wealso would like to thank Drs. Catherine Nguyen and RemiHoulgatte and Mrs Beatrice Loriod and Geneviève Victorerofrom the Unité INSERM ERM 206, Marseille, France, for thehelp and discussions and for the IMAGE MTB cDNA mouselibrary clones used in this study.ReferencesBertucci, F., Houlgatte, R., Granjeaud, S., et al., 2002. Prognosis of breastcancer and gene expression profiling using DNA arrays. Ann. N.Y.Acad. Sci. 975, 217–231.Eisen, M., Spellman, P., Brown, P., Botstein, D., 1998. Cluster analysisand display of genome-wide expression patterns. Proc. Natl. Acad.Sci. U.S.A 95, 14863–14868.Espanhol, A.R., Macedo, C., Junta, C.M., et al., 2003. Gene expressionprofiling during thymus ontogeny and its association with TRVB8-DB2.1 rearrangements of inbred mouse strains. Mol. Cell Biochem.252, 223–228.Espanhol, A.R., Cardoso, R.S., Junta, C.M., et al., 2004. Large scalegene expression analysis of CBA/J mouse strain fetal thymus usingcDNA-array hybridizations. Mol. Cell. Biochem. 206, 65–68.Feske, S., Giltnane, J., Dolmestsch, R., et al., 2001. Gene regulationmediated by calcium signals in T lymphocytes. Nat. Immunol. 2,316–324.Feske, S., Okamura, H., Hogan, P.G., et al., 2003. Ca2+/calcineurin signalingin cells of the immune system. Biochem. Biophys. Res. Commun.311, 1117–1132.Fink, P.J., McMahan, C.J., 2000. Lymphocytes rearrange, edit and revisetheir antigen receptors to be useful yet safe. Immunol. Today 21,561–566.Fugmann, S.D., 2002. Breaking the seal. Nature 416, 691–694.Gill, J., Malin, M., Sutherland, J., et al., 2003. Thymic generation andregeneration. Immunol. Rev. 195, 28–50.Heissmeyer, V., Macian, F., Im, S.H., et al., 2004. Calcineurin imposesT-cell unresponsiveness through targeted proteolysis of signaling proteins.Nat. Immunol. 5, 238–240.Junta, C.M., Passos, G.A.S., 1998. Emergence of TCR- V(D)J recombinationand transcription during thymus ontogeny of inbred mousestrains. Mol. Cell. Biochem. 187, 67–72.Lefranc, M.P., Lefranc, G., 2001. The T-Cell Receptor Facts Book, firsted. Academic Press, Suffolk.Macedo, C., Junta, C.M., Passos, G.A.S., 1999. Onset of T-cell receptorV8.1 and D2.1 V(D)J recombination during thymus developmentof inbred mouse strains. Immunol. Lett. 69, 371–373.Mak, T.W., Penninger, J.M., Ohashi, P.S., 2001. Knockout mice: aparadigm shift in modern immunology. Nat. Rev. Immunol. 1, 11–19.Muegge, K., Vila, M.P., Durum, S.K., 1993. Interleukin-7: a cofactor forV(D)J rearrangement of the T-cell receptor gene. Science 261, 93–95.Nguyen, C., Rocha, D., Granjeaud, S., et al., 1995. Differential geneexpression in the murine thymus assayed by quantitative hybridizationof arrayed cDNA clones. Genomics 29, 207–215.Quackenbush, J., 2002. Microarray data normalization and transformation.Nat. Genet. Supp. 32, 496–501.Rugh, R., 1968. The Mouse. Its Reproduction and Development, first ed.Burgess Publishing Company, Edina, MN, USA.Saha, S., Bardelli, A., Buckhaults, P., et al., 2001. A phosphatase associatedwith metastasis of colorectal cancer. Science 294, 1343–1346.Shortman, K., Wu, L., 1996. Early T lymphocyte progenitors. Annu. Rev.Immunol. 14, 29–47.Sollof, R.S., Wang, T.G., Dempsey, D., et al., 1997. Interleukin-7 inducesTCR gene rearrangement in adult marrow-resident murine precursorT-cells. Mol. Immunol. 34, 453–462.Tusher, V.G., Tibshirani, R., Chu, G., 2001. Significance analysis of microarraysapplied to the ionizing radiation response. Proc. Natl. Acad.Sci. U.S.A 98, 5116–5121.Verdeil, G., Puthier, D., Nguyen, C., 2002. Gene profiling approach toestablish the molecular bases for partial versus full activation of naïveCD8 T lymphocytes. Ann. N.Y. Acad. Sci. 975, 68–76.