X-ray irradiation selectively kills thymocytes of different stages and impairs the maturation of donor-derived CD4+CD8+ thymocytes in recipient thymus
نویسندگان
چکیده
The aim of the present study was to determine whether the sensitivity of thymocytes to X-ray radiation depends on their proliferative states and whether radiation impairs the maturation of donor-derived thymocytes in recipient thymus. We assigned 8-week-old C57BL/6J mice into three treatment groups: 1) untreated; 2) X-ray radiation; 3) X-ray radiation plus bone marrow transplantation with donor bone marrow cells from transgenic mice expressing enhanced green fluorescent protein (GFP) on a universal promoter. After 4 weeks, the size of the thymus, the number and proliferation of thymocytes and ratios of different stage thymocytes were analyzed by immunohistochemistry and flow cytometry. The results showed that: 1) CD4(+)CD8(+) thymocytes were more sensitive to X-ray radiation-induced cell death than other thymocytes; 2) the proliferative capacity of CD4(+)CD8(+) thymocytes was higher than that of other thymocytes; 3) the size of the thymus, the number of thymocytes and ratios of thymocytes of different stages in irradiated mice recovered to the normal level of untreated mice by bone marrow transplantation; 4) the ratio of GFP-positive CD4(+)CD8(+) thymocytes increased significantly, whereas the ratio of GFP-positive CD4(+) or CD8(+) thymocytes decreased significantly. These results indicate that the degree of sensitivity of thymocytes to X-ray radiation depends on their proliferative states and radiation impairs the maturation of donor-derived CD4(+)CD8(+) thymocytes in recipient thymus.
منابع مشابه
Enhancement of activation-induced cell death by fibronectin in murine CD4+ CD8+ thymocytes.
Development of T cells in the thymus is achieved through the interactions of thymocytes with their microenvironments. This study focused on the function of fibronectin (FN), a major extracellular matrix molecule in the thymus, in the cell death induced by activation via the T-cell antigen receptor. FN alone did not increase cell death in murine thymocytes above the baseline level, but it signif...
متن کاملRegulation of pre-T cell receptor (pT alpha-TCR beta) gene expression during human thymic development
In murine T cell development, early thymocytes that productively rearrange the T cell receptor (TCR) beta locus are selected to continue maturation, before TCR alpha expression, by means of a pre-TCR alpha- (pT alpha-) TCR beta heterodimer (pre-TCR). The aim of this study was to identify equivalent stages in human thymocyte development. We show here that variable-diversity-joining region TCR be...
متن کاملFrom pre-DP, post-DP, SP4, and SP8 Thymocyte Cell Counts to a Dynamical Model of Cortical and Medullary Selection
Cells of the mature αβ T cell repertoire arise from the development in the thymus of bone marrow precursors (thymocytes). αβ T cell maturation is characterized by the expression of thousands of copies of identical αβ T cell receptors and the CD4 and/or CD8 co-receptors on the surface of thymocytes. The maturation stages of a thymocyte are: (1) double negative (DN) (TCR(-), CD4(-) and CD8(-)), (...
متن کاملCytosolic Sequestration of Prep1 Influences Early Stages of T Cell Development
OBJECTIVE Prep1 and Pbx2 are the main homeodomain DNA-binding proteins of the TALE (three amino acid loop extension) family expressed in the thymus. We previously reported reduced Pbx2 expression and defective thymocyte maturation in Prep1 hypomorphic mice. To further investigate the role of this homeodomain DNA-binding protein in T cell development, we generated transgenic mice expressing the ...
متن کاملCutting edge: developmental switches in chemokine responses during T cell maturation.
We show that developmental transitions during thymocyte maturation are associated with dramatic changes in chemotactic responses to chemokines. Macrophage-derived chemokine, a chemokine expressed in the thymic medulla, attracts thymocytes only during a brief window of development, between the late cortical and early medullary stages. All medullary phenotypes (CD4 or CD8 single positive) but not...
متن کامل