Thymus Migration and Dendritic Cell Behavior in the Stromal Cell Networks Regulate Thymocyte

نویسندگان

  • Marc Bajenoff
  • Stephanie L. Sanos
  • Jonathan Nowak
  • Mathieu Fallet
چکیده

After entry into thymus, T cell progenitors migrate in the cortex and the medulla while completing their education. Recent reports have documented the dynamic and tortuous behavior of thymocytes. However, other than chemokines and/or segregated thymic substrates, the factors contributing to the dynamic patterns of thymocyte movement are poorly characterized. By combining con-focal and dynamic two-photon microscopy, we demonstrate that thymocytes continuously migrate on thymic stromal cell networks. In addition to constituting " roads " for thymocytes, we observed that these networks also provide a scaffold on which dendritic cells attach themselves. These results highlight the central role of stromal microanatomy in orchestrating the multiple cellular interactions necessary for T cell migration/development within the thymus. T he thymus supports the sequential steps leading to T cell maturation and selection (1). Lymphoid progenitors enter the thymus at the corticomedullary junction, where they migrate outward toward the cortex as CD4 2 CD8 2 double-negative cells. In the cortex, double-negative cells further mature into CD4 + CD8 + double-positive (DP) cells upon rearrangement of their TCR band a-chains. Upon completion of the positive selection process, DP cells become either CD4 + CD8 2 or CD4 2 CD8 + single-positive (SP) cells and migrate to the medulla, where negative selection occurs. At the end of this selection process, mature T cells are exported to the periphery. A key question regarding thymocyte behavior within the thymus is how thymocyte migration is controlled within this densely packed environment. Thymi have a highly organized architecture composed of distinct cellular compartments and structures, at the heart of which lies a nonhematopoietic cell backbone (2). Among the cells that are critical for generating this backbone are various thymic stromal cells (TSCs), including cortical thymic epithelial cells (cTEC) and medullary epithelial cells (mTEC) as well as nonepithelial stromal cells (1). It is well established that during T cell development, an efficient cross-talk between thymocytes and TSCs is mandatory for their successful maturation (3). In the cortex, DP thymocytes crawl through the cortical environment, seeking to encounter self-MHC–peptide complexes expressed by various TSCs, including cTECs (4). In the medulla, mTECs express the transcription factor autoimmune regulator protein, which regulates the expression of peripheral tissue Ags, a critical step in the establishment of central tolerance as autoimmune regulator–deficient mice present a defined profile of autoimmune diseases (5). To complete thymocyte education, TSCs also provide chemical cues to them. As an example, SP …

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تاریخ انتشار 2011