Doctor of Philosophy
Anatomy & Neurobiology
Jack L. Haar
The suppression of the immune response in senescent animals, including humans, is not complete and may be ameliorated by specific interventions. Previous studies have suggested that the replacement of thymus factors lost with age may rejuvenate senescent immune function. Similarly, exogenous growth hormone has been reported to improve senescent immune function in certain mammals. Other studies with the immunomodulator PSK claim to restore tumor-induced immunosuppression even in aged mice. This project investigated the abilities of thymus supernatant, ovine growth hormone, and PSK to rejuvenate different
parameters of the senescent immune response.
In the first series of experiments, erythroid depleted bone marrow cells from 3 month and 24 month old CBA (Thy 1.2) mice were given to irradiated ARR (Thy1.1) mice and allowed
to repopulate for 30 days. Flow cytometry analysis using x mAb Thy 1.1 and Thy 1.2 revealed that the old bone marrow was deficient in its ability to repopulate the thymus. Subsequent experiments revealed that treatment of the old bone marrow with thymus supernatant, made from neonatal thymus cultures, could restore the thymus repopulating ability of these cells.
The second part of this project investigated the reported ability of growth hormone to rejuvenate the age-involuted thymus and senescent immune response. Limited success was achieved using subcutaneous timed-release pellets containing ovine growth hormone. Twenty-four month old mice treated in this manner for 8 weeks demonstrated larger thymuses with nearly normal thymus morphology, i.e. distinct cortical and medullary regions. Various assays of cellular immune function exhibited no improvement.
PSK injections every other day injections of 18 month old mice, for one month, resulted in an increase in splenic mass when compared to saline treated age—matched controls. There was no improvement in the thymus morphology or in the cellular immune function of the treated animals.
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