Expression of CD70 during Thymus Regeneration in the Rat

Kim, Sung Min; Kim, Mi Na; Lee, Hee Woo; Kim, Bong Seon; Kim, Jae Bong; Yoon, Sik

Abstract

The thymus is the central lymphoid organ for development of bone marrow-derived precursor cells into mature T-cells. The thymic stroma provides the specialized microenvironment for the proliferation, differentiation, and maturation of the immature T-cells, thymocytes. The CD27 is a tumor necrosis factor (TNF) receptor family member whose expression is limited to cells of the lymphoid lineage. CD70, the ligand of CD27, is a TNF related trans-membrane protein induced upon activation on T and B cells, dendritic cells and macrophages. CD70/CD27 interaction plays a key role in T dependent B cell responses and is responsible for plasma cell differentiation. This study was performed to investigate the expression of CD70 during regeneration following acute involution induced by cyclophosphamide (CY) in the rat thymus using RT-PCR analysis and single and double immunohistochemistry. The results from RT-PCR analysis showed that CD70 is expressed in mouse thymic medullary interdigitating (IDC)-like cells (MDC), DC2.4 and Raw264.7 but not expressed in the mouse thymic epithelial cells (subcapsular/cortex epithelial cells, cortical epithelial cells and medullary epithelial cells). Interestingly, upregulation of CD70 expression was observed in the thymic stromal cells and thymocytes isolated from rat thymus during thymus regeneration. Furthermore, immunohistochemistry demonstrated that CD70 was mainly expressed in the ED1 positive macrophages predominantly in the thymic cortex both in the normal thymus and during thymus regeneration. In line with the data obtained by biochemical analysis, CD70 immunoreactive macrophages is increased both in number and in size during thymus regeneration. Thus, the results of the present study suggest that CD70 expressed on the thymic macrophages could play a role in the development of new T cells to replace T cells damaged by cyclophosphamide treatment during thymus regeneration.