X-ray irradiation selectively kills thymocytes of different stages and impairs the maturation of donor – derived CD4 +CD8 + thymocytes in recipient thymus

Jinbo Li

doi:10.7555/jbr.26.20120003

Abstract

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 immunohisto-chemistry 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 thymo-cytes of different stages in irradiated mice recovered to the normal level of untreated mice by bone marrow trans-plantation; 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.

Highlights

T-cell development in the thymus is a complex process
The numbers of DP, DN, CD4-SP and CD8-SP thymocytes decreased significantly in the irradiated mice to 7.9%, 23.6%, 40.2% and 80.3% of untreated mice, respectively (Table 1). These results revealed that all different stage thymocytes could be affected when exposed to irradiation, and DP thymocytes were the most severely affected while other thymocytes were less affected
Radiosensitivity of thymocytes at different stage depends on their proliferative states Previous studies have reported that DNA doublestrand breaks constitute the most dangerous type of DNA damage induced by ionizing radiation, and genomic instability induced by perturbed recombination in cancer cells make them sensitive to ionizing irradiation[13]

Summary

Introduction

T-cell development in the thymus is a complex process. CD4- CD8- double-negative (DN) thymocytes develop from early thymic progenitors located in the subcapsular zone (SCZ), and advance toCD4+CD8+ double-positive (DP) cells as they meander through the cortex. T-cell development in the thymus is a complex process. CD4- CD8- double-negative (DN) thymocytes develop from early thymic progenitors located in the subcapsular zone (SCZ), and advance to. CD4+CD8+ double-positive (DP) cells as they meander through the cortex. *Corresponding author: Dengshun Miao, Ph.D., The Research Center for Bone and Stem Cells, Department of Human Anatomy, Nanjing Medical University, Nanjing, Jiangsu 210029, China. Negative selection is required for eliminating self-reactive thymocytes. Mature thymocytes in the medulla egress from the thymus to the blood stream and migrate to the peripheral lymphoid organs[1,2]

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