Ontogeny of Immunity in Frogs/Metamorphic Changes

小行星9421349 南非爪蟾的变态导致免疫系统的显著变化。 其特征是胸腺和脾脏明显退化，随后在变态后期出现显著的淋巴细胞扩增。 在一些其他两栖类和爬行类物种中观察到季节性的胸腺退化，并且在一些脊椎动物物种中观察到衰老。 在大多数胸腺退化的例子中，原因还没有很好的定义。 皮质类固醇激素（CH）已被牵连，但仔细的研究与生理浓度的天然激素和特定的激素受体拮抗剂尚未完成。 为了确定CH是否是爪蟾变态时胸腺退化和淋巴细胞数量下降的原因，将测试两种特异性CH受体拮抗剂。 体外研究将确定这些化合物在该系统中的有效性并确定有效浓度范围。 体内研究旨在抑制CH与其受体的结合，从而抑制可能的类固醇诱导的细胞死亡。 CH诱导细胞死亡的可能机制是程序性细胞死亡或凋亡。 为了研究这个问题，将在变态前、变态期间和变态后的几个阶段测定对照青蛙和CH-拮抗剂处理青蛙的胸腺和脾细胞群中的自发细胞凋亡率。 如果CH诱导的细胞凋亡是细胞衰退的机制，那么它应该被CH拮抗剂抑制。 如果胸腺细胞和脾细胞数量的下降不是由于CH诱导的细胞凋亡，则可能是由于变质高潮期间前体迁移和扩张速率降低。 为了研究这个问题，移民和扩张的二倍体（2N）前体到植入的三倍体（3 N）胸腺的速度将在高潮进行研究，并与观察到的premetamorphic和postmetamorphic阶段进行比较。 总的来说，这些研究将更精确地确定在变态胸腺细胞死亡和更换的动力学。 年轻的变性后青蛙的生存可能取决于它们对蝌蚪遇到的病原体的记忆反应。 因此，我们想知道蝌蚪淋巴细胞在变性后的时期中持续到什么程度。 蝌蚪T细胞与T细胞表型不同，因为它们不表达II类主要组织相容性复合体（MHC）抗原。 几个实验的目的是了解蝌蚪T细胞是否坚持通过变态和保留其蝌蚪表型或成为成人样和表达II类MHC。 这些实验将提供有关发育过程中免疫系统调节以及皮质类固醇激素在程序性细胞死亡中作用的信息 *

9421349 Rollins-Smith Metamorphosis in the South African clawed frog, Xenopus laevis, results in significant changes in the immune system. It is characterized by a striking involution of the thymus and spleen followed by significant lymphocyte expansion in the postmetamorphic period. Thymus involution is observed seasonally in some other amphibian and reptilian species, and with aging in a number of vertebrate species. In most of these examples of thymus involution, the causes are not well defined. Corticosteroid hormones (CH) have been implicated, but careful studies with physiological concentrations of natural hormones and specific hormone- receptor antagonists have not been done. To determine whether CH are responsible for thymus involution and the decline in numbers of lymphocytes at metamorphosis in Xenopus, two specific CH receptor antagonists will be tested. In vitro studies will establish the effectiveness of these compounds in this system and determine effective concentration ranges. In vivo studies are designed to inhibit binding of CH to their receptors and thus inhibit possible steroid-induced cell death. The likely mechanism of CH-induced cell death is programmed cell death or apoptosis. To examine this question, the rates of spontaneous apoptosis in the thymus and spleen cell populations of control frogs and frogs treated with CH- antagonists will be determined at several stages before, during, and after metamorphosis. If CH-induced apoptosis is a mechanism of cell decline, it should be inhibited by the CH-antagonists. If the decline in thymocyte and splenocyte numbers in not due to CH-induced apoptosis, it may be due to a decreased rate of precursor immigration and expansion during metamorphic climax. To examine this question, the rate of immigration and expansion of diploid (2N) precursors into an implanted triploid (3N) thymus will be studied at climax and compared with that observed at premetamorphic and postmetamorphic stages. C ollectively, these studies will more precisely define the dynamics of cell death and replacement in the thymus at metamorphosis. Survival of young postmetamorphic frogs might depend on their ability to mount a memory response to a pathogen encountered as a tadpole. Therefore, we would like to know to what extent tadpole lymphocyted persist in the postmetamorphic period. Tadpole T cells differ phenotypically from T cells because they do not express class II major histocompatibility complex (MHC) antigens. Several experiments are designed to learn whether tadpole T cells persist through metamorphosis and retain their tadpole phenotype or become adult-like and express class II MHC. %%% These experiments will provide information about the regulation of the immune system during development as well as the role of corticosterid hormones in programmed cell death ***