Immunohistochemical evidences showing the presence of thymulin containing cells located in involuted thymus and in peripheral lymphoid organs (original) (raw)
Related papers
Annals of the New York Academy of Sciences, 2009
Thymulin is a thymic hormone exclusively produced by the thymic epithelial cells. It consists of a nonapeptide component coupled to the ion zinc, which confers biological activity to the molecule. After its discovery in the early 1970s, thymulin was characterized as a thymic hormone involved in several aspects of intrathymic and extrathymic T cell differentiation. Subsequently, it was demonstrated that thymulin production and secretion is strongly influenced by the neuroendocrine system. Conversely, a growing core of information, to be reviewed here, points to thymulin as a hypophysotropic peptide. In recent years, interest has arisen in the potential use of thymulin as a therapeutic agent. Thymulin was shown to possess anti-inflammatory and analgesic properties in the brain. Furthermore, an adenoviral vector harboring a synthetic gene for thymulin, stereotaxically injected in the rat brain, achieved a much longer expression than the adenovirally mediated expression in the brain of other genes, thus suggesting that an anti-inflammatory activity of thymulin prevents the immune system from destroying virus-transduced brain cells. Other studies suggest that thymulin gene therapy may also be a suitable therapeutic strategy to prevent some of the endocrine and metabolic alterations that typically appear in thymus-deficient animal models. The present article briefly reviews the literature on the physiology, molecular biology, and therapeutic potential of thymulin.
Physiology and Therapeutic Potential of the Thymic Peptide Thymulin
Current Pharmaceutical Design, 2014
Thymulin is a thymic hormone exclusively produced by the epithelial cells of the thymus. After its discovery and initial characterization in the '70s, it was demonstrated that the production and secretion of thymulin are strongly influenced by the neuro-endocrine system. Conversely, a growing body of evidence, to be reviewed here, suggests that thymulin is a hypophysiotropic peptide. Additionally, a substantial body of information pointing to thymulin and a synthetic analog as anti-inflammatory and analgesic peptides in the central nervous system brain and other organs will be also reviewed. In recent years, a synthetic DNA sequence encoding a biologically active analog of thymulin, metFTS, was constructed and cloned in a number of adenovectors. These include bidirectional regulatable Tet-Off vector systems that simultaneously express metFTS and green fluorescent protein and that can be down-regulated reversibly by the addition of the antibiotic doxycycline. A number of recent studies indicate that gene therapy for thymulin may be an effective therapeutic strategy to prevent some of the hormonal and reproductive abnormalities that typically appear in congenitally athymic (nude) mice, used as a suitable model of neuroendocrine and reproductive aging. Summing up, this article briefly reviews the publications on the physiology of the thymulin-neuroendocrine axis and the anti-inflammatory properties of the molecule and its analog. The availability of novel biotechnological tools should boost basic studies on the molecular biology of thymulin and should also allow an assessment of the potential of gene therapy to restore circulating thymulin levels in thymodeficient animal models and eventually, in humans.
Thymulin and the neuroendocrine system
Peptides, 2004
Thymulin is a thymic hormone exclusively produced by the thymic epithelial cells. It consists of a nonapeptide component coupled to the ion zinc, which confers biological activity to this molecule. After its discovery in the early 1970, thymulin was characterized as a thymic hormone involved in several aspects of intra-and extrathymic T-cell differentiation. Subsequently, it was demonstrated that thymulin production and secretion is strongly influenced by the neuroendocrine system. Conversely, an emerging core of information points to thymulin as a hypophysotropic peptide. Here we review the evidence supporting the hypothesis that thymulin is an important player in the hypophyso-thymic axis.
The Thymus-Neuroendocrine Axis
Annals of The New York Academy of Sciences, 2009
Thymulin is a thymic hormone exclusively produced by the thymic epithelial cells. It consists of a nonapeptide component coupled to the ion zinc, which confers biological activity to the molecule. After its discovery in the early 1970s, thymulin was characterized as a thymic hormone involved in several aspects of intrathymic and extrathymic T cell differentiation. Subsequently, it was demonstrated that thymulin production and secretion is strongly influenced by the neuroendocrine system. Conversely, a growing core of information, to be reviewed here, points to thymulin as a hypophysotropic peptide. In recent years, interest has arisen in the potential use of thymulin as a therapeutic agent. Thymulin was shown to possess anti-inflammatory and analgesic properties in the brain. Furthermore, an adenoviral vector harboring a synthetic gene for thymulin, stereotaxically injected in the rat brain, achieved a much longer expression than the adenovirally mediated expression in the brain of other genes, thus suggesting that an anti-inflammatory activity of thymulin prevents the immune system from destroying virus-transduced brain cells. Other studies suggest that thymulin gene therapy may also be a suitable therapeutic strategy to prevent some of the endocrine and metabolic alterations that typically appear in thymus-deficient animal models. The present article briefly reviews the literature on the physiology, molecular biology, and therapeutic potential of thymulin.
Histochemical and molecular overview of the thymus as site for T-cells development
Progress in Histochemistry and Cytochemistry, 2008
The thymus represents the primary site for T cell lymphopoiesis, providing a coordinated set for critical factors to induce and support lineage commitment, differentiation and survival of thymus-seeding cells. One irrefutable fact is that the presence of non-lymphoid cells through the thymic parenchyma serves to provide coordinated migration and differentiation of T lymphocytes. Moreover, the link between foetal development and normal anatomy has been stressed in this review. Regarding thymic embryology, its epithelium is derived from the embryonic endodermal layer, with possible contributions from the ectoderm. A series of differentiating steps is essential, each of which must be completed in order to provide the optimum environment for thymic development and function. The second part of this article is focused on thymic T-cell development and differentiation, which is a stepwise process, mediated by a variety of stromal cells in different regions of the organ. It depends strongly on the thymic microenvironment, a cellular network formed by epithelial cells, macrophages, dendritic cells and fibroblasts, that provide the combination of cellular interactions, cytokines and chemokines to induce thymocyte precursors for the generation of functional T cells. The mediators of this process are not well defined but it has been demonstrated that some interactions are under neuroendocrine control. Moreover, some studies pointed out that reciprocal signals from developing T cells also are essential for establishment and maintenance of the thymic microenvironment. Finally, we have also highlighted the heterogeneity of the lymphoid, non-lymphoid components and the multi-phasic steps of thymic differentiation. In conclusion, this review contributes to an understanding of the complex mechanisms in which the foetal and postnatal thymus is involved. This could be a prerequisite for developing new therapies specifically aimed to overcome immunological defects, linked or not-linked to aging.
Journal of Immunological Methods, 1990
A new, specific and sensitive radioimmunoassay, using a polyclonal antiserum raised in rabbits, is described for quantitating plasma thymulin. As little as 300 fg thymulin can be measured in one assay tube. The method has been used to measure thymulin in human blood (umbilical vessel blood, 2191 + 123 fg/ml; children and adults up to the age of 20 years, 1499 + 119 fg/ml; and adults between 21-65 years, 371 + 18 fg/ml). There is a highly significant decrease within these three groups (P < 0.001 by one way analysis of variance). Also plasma thymulin levels were determined in rats (601 + 127 fg/ml) and in pooled plasma samples from mice (638 + 56 fg/ml). No thymulin was detected in plasma obtained from nude rats, nude mice and thymectomised mice. These results show that the radioimmunoassay described here is a useful quantitative tool for measuring plasma thymulin that will have applications in basic, applied and clinical research.