The Ultrastructure Of Newborn Yaks Thymus And The Expression Of CD4 And CD8α In Lymphoid Organs Of Different Age Yaks

Aging of the immune system, or “immunosenescence”, is associated with both a marked reduction in responsiveness as well as functional dysregulation. These changes have been implicated in the increased morbidity and mortality of the elderly population from infectious disease, and may also play a role in autoimmunity and cancer. However many vaccines are not as effective in generating protective antibodies in older individuals. Though marginal alterations in B lymphocytes are apparent, the dramatic decline in humoral and cell mediated responses is predominantly the consequence of alterations in the T-cell compartment. Firstly, this review focuses on the CD8+ T-cell subset. Age-related changes in thymic function and involution, cellular homeostasis and lifespan, population shifts, T-cell activation, the process of replicative senescence, and oligoclonal expansions are discussed in terms of their effect on CD8 expression and the function of CD8+ T cells. Age-associated alterations in CD4+ T cells and antigen-presenting cells are mentioned insofar as these cells affect CD8+ T-cell activation and function. Distinct patterns of immunosenescence in humans and mice are also noted. Secondly, this review focuses on the CD4+ T-cell subset. CD4+ T cells, through their B cell helper functions, play a central role in the humoral response. We summarize the qualitative and quantitative changes of CD4 expression that arise with aging. We also summarize the age-related intrinsic defects that impact CD4+ T cell functions. Overall, understanding how aging influences the expression of T cell markers and impairs CD4+ and CD8+ T cell functions are of critical importance to design new immunization and treatment strategies targeted to the elderly population. It would provide fundamental data for timely immunization, the pathogenesis and disease prevention.(1) Thymus was considered as a central lymphoid organ due to its primary role as being the initial site for differentiation and maturation of T lymphocytes. In this study, the ultrastructural characteristics of the thymus in newborn yaks(Bos grunniens) was observed using electron microscopy. The results demonstrated the structure of thymus in newborn yaks devloped well. And a supporting framework of epithelial-reticular cells with long branching cytoplasmic processes joined by desmosomes. In the interstices of the epithelial-reticular cell processes lie lymphocytes, dentritic cells, macrophages and rare plasmocytes. The lymphocytes mitosis was often detected in cortex. And the shape of medulla lymphocytes was various. And the nucleus shows large indentation with large clumps of peripheral heterochromatin. Macrophages are most numerous in the cortex where they often contain lysosome and phagocytized nuclear debris. TDCs containing an irregularly shaped nucleus and branched cytoplasmic projections that were interdigitated by the surrounding thymocyte cytoplasmic processes were seen. The article also described the ultrastructure of plasma cells, eosnophils and neutrophils in the thymus of neonatal yaks. The results suggested the thymus in newborn yaks had developed well, which similared with human. It would provide morphological datas for futher study to the thymic function and the development of T lymphocytes, and also add new datas to comparison histology.(2) CD4 is a membrane-bound glycoprotein found on T cells, and also an important surface marker of helper T lymphocyte. This molecule widely involves in recognition of specific antigens in association with major histocompatibility complex II(MHC II) molecules and transmembrane signal transduction. Expression of CD4 is critical for cell- mediated immune response and defense mechanisms. In this study, the yak(Bos grunniens) CD4 open reading frame(ORF) was cloned and sequenced using RT-PCR. And CD4 m RNA and protein expression in the thymus, spleen, mesenteric lymph nodes and haemal nodes of newborn(7-9 days; n = 5), half-year-old(5-7 months; n = 5) and adult(3-4 year; n = 5) yaks were determined by q RT-PCR(quantitative Real- time PCR), Western blots and immunohistochemical method. The results showed that yak CD4 ORF contained 1 188 bp, encoded 396 amino acids. The c DNA sequences of yak CD4 revealed significant homology with Bos taurus. The results of q RT-PCR and Western blots showed that CD4 m RNA and protein widely expressed in lymphoid organs, and CD4 expression in the thymus were always higher than those of the spleen, haemal node and mesenteric lymph node(P<0.05). During development, the expression of CD4 in yaks lymphoid organs were decreased in an age-related way. Moreover, the m RNA and protein expression of CD4 were significantly greater in newborn and half-year-old than those found in the adult yaks lymphoid organs, respectively(P<0.05). The immunohistochemical results showed that the CD4+ cells were distributed in the cotex and medulla of yak thymus. In the spleen, many CD4+ cells were located in the periarteriolar lymphoid sheaths and red pulp. Moreover CD4+ cells in mesenteric lymph nodes and haemal nodes were mainly presented in the mantle zone, the cords and sinus of medulla. The results indicated the development of CD4 were changed in an decreased way, and the thymic expression may influence the CD4 expression levels of secondary lymphoid tissues. Then haemal nodes might have similar functions as the mesenteric lymph nodes and spleen. This study would contribute to our knowledge of the function and mechanism of CD4 in the cell-mediated immune response. It would also provide fundamental datas for immunogenetics and immunobiology, and bring a new insight into timely immunization, the pathogenesis and disease prevention.(3) CD8α is an important surface marker of cytotoxic T lymphocyte. This molecule is critical for cell-mediated immune response and defense mechanisms, widely involved in recognition of specific antigens in association with MHCI molecules and transmembrane signal transduction. In this study, the yak(Bos grunniens) CD8α was cloned using RT-PCR, and the expression of CD8α m RNA and protein in the major immune organs(thymus, spleen, mesenteric lymph nodes and haemal nodes) of newborn(7-9 days; n = 5), half-year-old(5-7 months; n = 5) and adult(3-4 year; n = 5) yaks were detected by means of quantitative real-time fluorescence quantitative PCR, Western blots and immunohistochemical methods. The RT-PCR results showed the coding sequence of yak CD8α contained 729 bp, encoded for 243 amino acids. The c DNA sequences of yak CD8α revealed significant homology with Bos taurus. The quantitative real-time fluorescence quantitative PCR and Western blots results showed that CD8α m RNA and protein were widely expressed in immune organs, and CD8α m RNA and protein in the thymus were always higher than those of the spleen, haemal node and mesenteric lymph node(P<0.05). During development, the expression of CD8α in yaks lymphoid organs were increased in an age-related way. Moreover, the m RNA and protein expression of CD8α were significantly greater in lymphoid organs of half-year-old and adult yaks than those found in the neonates, respectively(P<0.05). Additionally, the immunohistochemical results showed the CD8α+ cells were distributed in the cotex and medulla of yak thymus. In the spleen, many CD8α+ cells were located in the periarteriolar lymphoid sheaths, the cords and sinus of red pulp. Moreover CD8α+ cells in mesenteric lymph nodes and haemal nodes were mainly presented in the mantle zone, the cords and sinus of medulla. The results indicated the development of CD8α in yaks lymphoid organs were increased in an age-related way, and the thymic CD8α expression might influence the CD8α expression level of secondary immune organs. Especially, CD8+ cells appeared in the follicles of yaks secondary lymphoid organs, which is different from other mammals. This study provided datas for futher study to immunologically-adaptive mechanisms under the plateau environment, and also provided new insights into timely immunization, the pathogenesis and disease prevention.