O papel modulador do gene AIRE - capes

227coincided (CBA/J) with expression of the RAG-1 and RAG-2 genes.In agreement with previous observations [17, 18] we observedthat the overall level of RAG-2 expression was lowerthan that of RAG-1 in Balb-c and C57Bl/6 mice, whereas theinverse situation was observed in CBA/J mice.Germline transcripts of TCRVβ were detected before theTCR β locus rearrangements [1, 19–22] and our results withthe CBA/J strain agree these observations. However, TCRVβwas one among the lesser transcribed genes.MHC-I and MHC-II displayed different expression patternsamong strains and there was a suggestion that theircontribution to the termination of TCR rearrangements isunlikely [23].The clustering of IL-1α, IL-1β, IL-2, IL-3, IL-4, IL-6, IFγand IL-2Rβ genes diverged among strains; however, weobserved a common tendency of their expression after (Balbc)and before RAG-1 and RAG-2 genes (C57Bl/6 and CBA/J strains).We were able to quantify the expression levels of all thesegenes implicated in T-cell proliferation, V(D)J recombinationor T-cell clonal deletion, such as MMTV(SW) retroviralsuperantigen, during thymus ontogeny (14–17 days p.c.) innewborn pups and adults. The onset of the TCRVβ8.1-Dβ2.1rearrangement in fetal thymus was correlated with a previousexpression of germline TCRVβ8.1 in the CBA/J strain(15–16 days p.c.). The most evident feature demonstrated wasthe kinetics of MMTV(SW) mRNA overexpression and parallelreduction of the TCRVβ8.1-Dβ2.1 rearrangement in the17 days p.c. thymus DNA of the of the CBA/J strain (Fig. 1),suggesting a susceptibility of this strain to the expression ofMMTV(SW) superantigen in combination with its geneticbackground, including MHC H-2 k , upon reduction of T-cellclones bearing the rearranged Vβ8.1 DNA segment, whilecoinciding with overexpression of IL-7 gene that plays a rolein T-cell proliferation.Expression of superantigen proteins from endogenousMMTV proviruses carried by mouse germline usually resultsin the deletion of self-reactive T-cells during negative selectionin the thymus and the elimination of T-cells required forinfection by specific milk-borne MMTVs [24, 25].Our data contribute to establishing a direct correlationbetween the different expression profiling, including cytokines,and backgrounds of the strains with evolution of TCRVβ8.1-Dβ2.1 rearrangements, of particular interest for characterizationof CBA/J mice, since the expression of these genes arenot typically studied in this strain.However, due to the complexity of this phenomenon involvingthe participation of a range of known and unknowngenes, our model-system with inbred mouse strains openperspectives for further studies on large-scale gene expressionprofiling using DNA-arrays.AcknowledgementsA.R.E., C.M.J. and R.S.C. are predoctoral fellows supportedby FAPESP (00/01705-8, 96/07847-1 and 00/09994-9, respectively),C.M. is a fellow from the Ludwig Institute forCancer Research (São Paulo) in the Human Cancer TranscriptSequencing Project. We thank the INSERM-FAPESP agreementwhich has permitted cooperation between the Brazilianand French groups. G.A.S.P. received grants from FAPESP(98/09789-4, 98/05584-9, 99/12135-9 and 00/12495-4).References1. Junta CM, Passos GAS: Emergence of TCRα/β V(D)J recombinationand transcription during ontogeny of inbred mouse strains. Mol CellBiochem 187: 67–72, 19982. Macedo C, Junta CM, Passos GAS: Onset of T-cell receptor Vβ8.1 andDβ2.1 V(D)J recombination during thymus development of inbredmouse strains. Immunol Lett 69: 371–373, 19993. Muegge K,Vila MP, Durum SK: Interleukin-7: A cofactor for V(D)Jrearrangement of the T-cell receptor gene. Science 261: 93–95, 19934. Sollof RS, Wang TG, Dempsey D, Jennings SR, Wolcott RM, ChervenakR: Interleukin 7 induces TCR gene rearrangement in adult marrowresidentmurine precursor T cells. Mol Immunol 34: 453–462, 19975. Candeias S, Muegge K, Durum SK: IL-7 receptor and V(D)J recombination:Trophic vs. mechanistic actions. Immunity 6: 501–508, 19976. 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