|
CD30 is first identified as a tumor marker for neoplastic cells of Hodgkins (HD) lymphoma. It is now known that CD30 can be expressed by a variety of cells, including activated T cells, macrophages, and other non-HD lymphoma cells. Its cognate ligand protein, CD30L, has also been identified. CD30L and CD30 belong to the TNF/NGF cytokine and TNFR/NGFR superfamily, respectively. Most members of this superfamily are known to work as a complex network in regulating cell proliferation, differentiation, survival or death. For example, interaction of CD30 and CD30L has pleiotrophic activity in mediating cell death, proliferation and differentiation. The study of CD30-deficient mice demonstrated an increased numbers of thymocytes. Further in vitro and in vivo studies revealed that CD30 is involved in the signaling of thymic negative selection in mouse thymus. Very little is known about the distribution of CD30 ligand and its correlation with receptor.The purpose of this study is to investigate the interaction of CD30 receptor and ligand in thymic negative selection. Using RT-PCR analysis, CD30 transcripts can be detected in mouse thymus up-to the 7th day of postnatal life, while the significant expression of CD30 ligand in thymus appeared only after two weeks. Flow cytometry study with 3-day- and 3-week-old mice, further confirmed an unparalleled expression of CD30 ligand and its receptor in pup thymus. Immunohistochemical staining was used to identify the cell types and localization for CD30 and CD30 ligand expression. In 7-day-old mouse, CD30 receptor is expressed in a small numbers of large cells that mainly located in the thymic medulla while little numbers signal of CD30 ligand was found at this stage of thymic cortex. However, CD30 ligand can be detected in most cortical thymocytes of 6-week-old mouse. The study of human embryos collected from miscarriages at 20∼24-week-gestation also supports the finding in mouse, that the expression of CD30 ligands was undetectable at this early stage and very few of CD30 receptors were expressed in the large cells within thymic medulla. My data demonstrated a temporal and unparalleled expression between CD30 receptor and its ligand, and a lack of expression of CD30 (as a receptor) in most thymocytes, indicating that CD30 ligand might not be directly responsible for negative selection in thymus. Further study is required to clarify the mechanism involved in CD30 signalings pathway in thymic T cell development.
|