thymic-factor--circulating and Atrophy

Suckling mice infected with reovirus type 2 showed a thymic atrophy followed by a marked suppression of the antibody, production to SRBC (a T cell dependent antigen) and bacterial LPS, when measured by the splenic PFC assay. The PFCs produced were sometimes less than 1% of uninfected control animals. Histologically the thymus was usually smaller than normal, and atrophy of the cortex and increased number of Hassal's bodies were observed. Number of nucleated cells in the thymus of infected mice showed 90% decrease as compared to uninfected mice. The spleen, although larger in size, showed depletion of lymphocytes from the thymus-dependent and follicular areas. No viral replication was detected in lymphatic organs using virological methods. Virus-infected mice transferred with the splenocytes or thymocytes from age-matched uninfected mice restored the antibody production against SRBC to normal levels. Thymocytes were more efficient than splenocytes in enhancing the antibody production in virus-infected mice. Injection of several different kinds of immunopotentiating agents enhanced the antibody production to SRBC, although LPS exacerbated the unresponsiveness. Thymic hormones such as FTS and TP5 enhanced antibody production to SRBC and LPS more efficiently than MDP. Flow cytometric analysis showed that percentage of CD4+ single positive cells was slightly increased in virus-infected mice treated with FTS, while there was no difference in the phenotypic distributions of thymocyte subpopulations among virus-infected mice, FTS-untreated and FTS-treated normal mice.

Topics: Age Factors; Animals; Animals, Suckling; Antibody Formation; Atrophy; Autoantibodies; Female; Immune Tolerance; Immunotherapy, Adoptive; Male; Mice; Mice, Inbred BALB C; Reoviridae; Reoviridae Infections; Spleen; Thymic Factor, Circulating; Thymopentin; Thymus Gland

Age-related features of structural and cytochemical changes in the brain cortical neurons were investigated in offspring of rats which were neurosensitized and received a course of timalin treatment during gestation. Course treatment with the drug prevented the development of dystrophic changes in cortical neurons, their death and decrease in cell density within the cortical layers. Timalin acted positive in terms of increase in protein content of the cellular nucleus and especially in the cytoplasm. These effects were more pronounced in aged animals. Possible mechanism of timalin action in neurosensitized mothers is discussed.

Topics: Adjuvants, Immunologic; Animals; Atrophy; Autoantibodies; Autoimmune Diseases; Brain; Cerebral Cortex; Female; Immunity, Maternally-Acquired; Neurons; Pregnancy; Rats; Thymus Hormones

The thymic epithelium, a major component of the thymic microenvironment, is a heterogeneous tissue bearing distinct monoclonal antibody-defined subsets. Among these, KL1+ cells represent a mouse medullary subpopulation characterized by high mol wt cytokeratin expression. Given the fact that thymic epithelial cells (TEC) express glucocorticoid receptors and that glucocorticoid hormones are known to modulate the expression of keratins, we decided to study the in vivo effects of hydrocortisone on KL1+ cells in normal and autoimmune mice. Within 24 h after a single injection of this steroid we observed a significant increase in the number of KL1+ cells. Interestingly, this effect was reversible and was no longer detected 7 days after treatment. Parallel studies analyzing the effects of hydrocortisone on the secretion of thymulin, a chemically defined thymic hormone revealed a transient decrease in serum levels of this hormone, but with different kinetics than the effects on KL1+ cells. Ontogenetic studies showed that the responsiveness of TEC to hydrocortisone, in terms of high mol wt cytokeratin expression, appeared late in fetal life and disappeared in aging animals. Importantly, aging, but also young adult, autoimmune mice were not responsive. In vitro experiments using a mouse TEC line confirmed the data observed in vivo demonstrating that the increase in KL1+ cells is a direct effect of hydrocortisone on TEC. The bulk of the data presently reported demonstrates that glucocorticoid hormone can act on TEC modulating the expression of both secretory and cytoskeletal protein families.

Topics: Aging; Animals; Atrophy; Autoimmune Diseases; Cell Count; Dose-Response Relationship, Drug; Epithelium; Hydrocortisone; Immunoblotting; Keratins; Kinetics; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Inbred NZB; Molecular Weight; Thymic Factor, Circulating; Thymus Gland

Adrenalectomy prevents thymic atrophy but not splenomegaly in mice implanted with Lewis Lung carcinoma cells. Surprisingly, the presence of the tumor does not lead to increased levels of corticosterone, which argues against an exclusive role of stress in the tumor-induced involution of the thymus. Interestingly, serum from tumor-bearing hosts in vitro displays strong cytolytic activity against normal syngeneic thymocytes. This thymocytotoxicity depends upon the stage of tumor development, i.e., the size of the local tumor, and is concomitant with the severe thymic atrophy. Treatment of donor mice with zinc chloride or excision of the local tumor, both of which have been shown to prevent this involution of the thymus, also abolishes the cytotoxic effect of the serum. The active component of the serum is a nonimmunoglobulin fraction of molecular weight greater than 25,000 Da. The possible mechanisms of tumor-dependent thymic atrophy as well as the in vivo relevance of this serum-mediated thymocytotoxicity are discussed.

Topics: Adrenalectomy; Animals; Antilymphocyte Serum; Atrophy; Carcinoma; Cell Count; Cell Survival; Corticosterone; Cytotoxicity, Immunologic; Female; Killer Cells, Natural; Lung Neoplasms; Mice; Mice, Inbred C57BL; Neoplasm Transplantation; Organ Size; Spleen; T-Lymphocytes; Thymic Factor, Circulating; Thymus Gland

Non-specific immunological modifications in mice during syngeneic gestation can be demonstrated. A dramatic transient thymic involution results from a significant reduction in the subpopulations of the thymic cortex with the remaining thymocytes being mainly medullary in nature. Response to PHA and Con A is greatly reduced in this pool which can normally be strongly stimulated. No suppressor cells or alteration in thymic epithelial function could be demonstrated. The unexpected low responsiveness of the remaining thymocytes was reversible after in vitro neuraminidase treatment. Meanwhile, MRL of thymocytes to allogeneic cell during syngenic gestation was not impaired.

Topics: Animals; Atrophy; Cells, Cultured; Concanavalin A; Female; Lymphocyte Activation; Lymphocyte Culture Test, Mixed; Mice; Mice, Inbred CBA; Mitosis; Neuraminidase; Phytohemagglutinins; Pregnancy; Pregnancy, Animal; T-Lymphocytes; Thymic Factor, Circulating; Thymus Gland