Precise analyses of the structure of the thymus for establishing details of the mechanisms underlying thymocyte proliferation and maturation.
Details of thymocyte proliferation and maturation are important for understanding the variability of T cell functions. The following aspects need to be clarified in this context: 1) Ascertaining why hematopoietic committed pre-T cells migrating in the blood stream are trapped and proliferate in the subcapsular region of the thymus. Further morphological and functional studies of stromal cells in situ in the thymus should be conducted. The factors responsible for thymocyte proliferation should be also analysed. 2) How phenotypic maturation of thymocytes takes place and how T-cell receptor (TCR) expression is processed and controlled. 3) Subsequently, how does the selection of thymocytes take place? Is negative selection in fact responsible for the unresponsiveness of the body to self antigens? Further morphological analyses of thymic epithelial cells, thymocytes themselves and macrophages need to be conducted, together with immunohistochemical analyses using many monoclonal antibodies directed against these cells and the extracellular matrix, in order to analyse the cellular dynamics and cell-to-cell interactions occurring in thymus tissues in situ. 4) How mature thymocytes migrate to the periphery: Perivascular structures and the cells accumulating in this space should be intensively analysed morphologically and phenotypically. Lymphatic structures related to the thymus tissues also remain to be studied. To understand these questions, several useful experimental systems can also be employed: 1) Phylogenetical analyses, 2) ontogenical analyses, 3) thymus tissues regenerating from radiation or thymotoxic drugs, 4) thymomas, and 5) thymus tissues from transgenic animals. These important problems could be further studied in such experimental models both morphologically and immunohistochemically, since many useful tools are now available for studies of phenotypic and other markers of thymocytes and thymic epithelial cells. Subsequently, further detailed analyses of thymic structures may shed more light on the mechanisms underlying thymocyte proliferation and maturation.
Fukumoto
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Department of Anatomy, Yamaguchi University School of Medicine, Ube, Japan.
D000818:Animals; D016923:Cell Death; D002454:Cell Differentiation; D002455:Cell Division; D002465:Cell Movement; D004848:Epithelium / Q000502:physiology; D005109:Extracellular Matrix / Q000502:physiology; D010802:Phylogeny; D013950:Thymus Gland / Q000033:anatomy & histology* / Q000187:drug effects / Q000254:growth & development / Q000528:radiation effects