Thymic size and T-cell function decrease with age, and it has not yet been possible to totally reverse this thymic atrophy and completely restore T-cell-dependent immune functions. In this study, GH3 pituitary adenoma cells, which secrete growth hormone and prolactin, were implanted subcutaneously into 16-and 22-month-old female Wistar-Furth rats and the rats were sacrificed approximately 2 months later. Only thymic remnants were detected in aged, non-implanted rats, but thymus glands were found in both the 18-and the 24-month-old rats that had been implanted with GH3 cells. Thymus glands from the GH3-implanted 18-month-old rats contained distinct cortical thymocytes and medullary epithelial cells. Depending on the concentration of phytohemagglutinin or concanavalin A, T-cell proliferative responses of splenocytes from these implanted rats were 2-to 5-fold greater than those of 18-month-old controls. At the optimal concentration of mitogen, proliferative responses to either lectin could be restored to those levels observed in splenocytes from 3-monthold Wistar-Furth females. Thymus glands from 24-month-old GH3-implanted rats contained more cortical thymocytes and fewer fat vacuoles than controls, but they were not totally reconstituted. No significant lectin-induced T-cell proliferative responses or IL-2 secretion were detected in 24-month-old control rats, but splenocytes from GH3-implanted rats showed augmented T-cell proliferative responses and increased synthesis of IL-2. Fluorescence-activated cell-sorter analysis of thymocytes revealed that 24-month-old rats implanted with GH3 cells had a higher proportion of lymphocytes with the Thy-1.1 and helper-T-cell phenotypes. These data show that it is possible to regenerate normal thymic tissue in situ and reverse the natural loss in cell-mediated immunity that occurs with aging.
Infection of murine splenocytes with Newcastle disease virus results in expression of the proopiomelanocortin gene as determined by dot and northern blot analysis of total cellular and poly(A)+ cytoplasmic RNA. These data provide the first evidence that the precursor protein for adrenocorticotropin and beta-endorphin can be synthesized by lymphoid cells.
Mild restraint of the domestic pig (Sus scrofa) caused activation of the hypothalamicpituitary-adrenal axis, atrophy of the thymus gland, and a significant reduction in cellmediated, delayed-type hypersensitivity reactions. Physiologic concentrations of cortisol s u p pressed, in vitro, phytohemagglutinin-and concanavalin A-induced proliferation of porcine thymocytes, splenocytes, and peripheral blood mononuclear cells, even though cortisol was only mildly cytolytic. These results extend the concept of an endocrine influence on regulation of cell-mediated immune events to species other than humans and rodents. Q 1984 Society for Experimental Biology and Medicine.
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