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O papel modulador do gene AIRE - capes

O papel modulador do gene AIRE - capes

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in the V(D)J recombination of T cell receptor <strong>gene</strong> segments (TRA, TRB, TRGand TRD) [13].The early fetal thymus has homo<strong>gene</strong>ous cell populations composed oflymphoid progenitors derived from the bone marrow, which is formed by <strong>do</strong>ublenegative(DN1), CD44 high CD25 + (DN2), CD44 low CD25 + (DN3), and CD44 lowCD25 - (DN4) thymocytes. During DN to CD4 + CD8 + <strong>do</strong>uble-positive (DP)transition, thymocytes relocate to the thymic cortical region, where most <strong>do</strong> notrecognize the available MHC molecules expressed by thymic stromal cells anddie as a result.The remaining DP thymocytes undergo negative selection occurring both inthe cortex and in medulla, leading to the deletion of autoreactive clones andfavoring MHC-restricted CD4 and CD8 single-positive T cells (CD4 + SP andCD8 + SP), which finally gain the periphery [14,15].In contrast, the newborn and adult thymus is the arrival place of newcolonizing precursors, which contribute to the formation of hetero<strong>gene</strong>ous cellpopulations, including macrophages and dendritic cells [16].Studies on temporal V(D)J recombination of TRA and TRB <strong>gene</strong>s [17,18] anddifferential expression of immune system-related <strong>gene</strong>s, such as interleukinsand the major histocompatibility complex (MHC) [19] during thymus ontogeny,showed that the <strong>gene</strong>tic background of different inbred mouse strains plays animportant role in the modulation of the emergence of T cell maturation.The cDNA microarray, as a high-throughput functional genomic technology,provides comparative analysis between the different phases of thymusontogeny, yielding quantitative expression data of hundreds or thousands of<strong>gene</strong>s in a single experiment. Research on <strong>gene</strong> expression during thymus238

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