| Vitamin A (retinol) and its biologically active derivatives (the retinoids) modulate a wide variety of biological processes including embryogenesis, proliferation and differentiation of many cell types. Vitamin A plays an important role in maintaining immunity. Recently, Increasing evidence suggests that vitamin A and its active derivatives, retinoic acid (RA), enhance the antibody response to T-cell dependent antigens, increase lymphocyte proliferation and cytokine production, inhibit apoptosis and maintain mucosal integrity. Physiologic concentrations of RA enhanced IgM production of cord-blood mononuclear cells (CBMC) stimulated with Cowan I strain Staphylococcus (SAC), but have no effect on the IgM synthesis of adult peripheral blood mononuclear cells. These results suggested that RA mediated immune response maybe age-related. RA is very likely involved in children's immune development, while there are few papers regarding this phenomenon, and the molecular mechanisms related to the biological effects of RA are not well defined. It is generally thought that these effects are mediated through retinoic acid receptors, a group of nuclear receptors involved in retinoic acid-mediated gene activation. The T lymphocytes, which are an important adaptive cellular component of the immune system, can both modulate the function of other immune cells and directly destroy cells infected with intrancellular pathogens. In the current study, we investigated the relationship between expression of retinoic acid receptors genes and T lymphocyte development, and attempted to elucidate the potential mechanisms of action of retinoic acid receptors on human T lymphocytes development.Part I Expression and distribution of retinoic acid receptors genes in children's thymusObjective: Retinoic acid controls the differentiation of a variety of cell types, although its role in influencing T cell development and the mechanisms potentially involved have not been thoroughly investigated. The thymus gland is a central lymphoid organ in which bone marrow-derived T cell precursors undergo differentiation, eventually leading to migration of positively selected thymocytes to theperipheral lymphoid organs. The effects of RA are mediated through retinoic acid receptors, a group of nuclear receptors involved in retinoic acid-mediated gene activation. Therefore ,developmental expression patterns of retinoic acid receptors in human thymus are important in elucidating the mechanisms of normal functions of retinoids and retinoids mediated immune responses .In this study, we investigated the expression and distribution of retinoic acid receptor genes in children's thymus, and evaluated their functions in the development of T lymphocyte. Methods: Thymus glands were obtained from 20 children, aged from 3 mouths to 5 years. The antisense ribo-probes of human RARα,RARβ,RARγ, RXRα,RXRβ,RXRγ were synthesized and labeled with DIG RNA labeling kit .In situ hybridization was performed on frozen thymus section. Immunohistochemistry staining for CD1a and CD3 were performed on the continueous frozen thymus section to show the relationship between retinoic acid receptor gene expression and T cell development. The real time quantitative RT-PCR assay was used to detect the retinoic acid receptor mRNA expression in thymus. Results : By using the In situ hybridization,we found that both expression of RARα and RARγ mRNA was seen in thymic cortex and medulla,the RARα mRNA highly expressed in the cortical region. The RXRα and RXRβ mRNA positive cells were found in the medulla of human thymus, mainly in the outer region of Hassall's corpuscles. Thymic cortex is positive for CD1a expression, whereas, CD3 expression was observed in the thymic medulla, highest in the outer region of Hassall's corpuscles. Furthermore, both RARβ and RXRγ mRNA expression were not detected in thymus. The real time quantitative RT-PCR analyses showed that the expression of RARα and RXRα mRNA were at a high level during the first year after birth, it dec... |
PDF Full Text Request