John R. Stevenson

John R. Stevenson

Associate Professor of Microbiology

Office: 52 Pearson Hall
Phone: (513) 529-5427
URL: Bugs'n'Drugs


Ph.D., Case Western Reserve University, 1972

Research Interests

During my research career at Miami University, I was interested in the effects of protein malnutrition on development and function of the immune system. Studies in my laboratory have shown that protein malnourished mice develop an immunodeficiency syndrome characterized by thymic atrophy that leads to depressed immune responsiveness. Development of this immunodeficiency syndrome is triggered by increased plasma corticosterone, which induces thymocyte apoptosis that results in thymic atrophy. As malnutrition continues, the number of T lymphocytes decreases in the blood and the spleen as well as in the thymus. This immunodeficiency syndrome is important to study because T cells play a pivotal role in generation and maintenance of the immune responses necessary for prevention of, and recovery from, infection. Current research in my laboratory is aimed at determining how this immunodeficiency syndrome develops and how it affects the functions of the immune system in host defense against infection.

We have shown that high levels of corticosterone induce apoptosis of immature thymic T cells to cause the thymic atrophy seen in protein malnourished mice. However, the thymic atrophy is not as rapid nor as severe as would be predicted based on the corticosterone levels in these mice. This is because apoptosis is somehow downregulated by heat shock proteins produced by these thymocytes in response to the stress of their protein deficiency. We are now investigating the mechanisms by which the heat shock proteins inhibit thymocyte apoptosis as well as the mechanisms by which corticosterone induces apoptosis in this system. These studies are facilitated by the use of silencing RNA and plasmid constructs encoding heat shock protein genes, flow cytometric analysis of apoptotic events, and intracellular flow cytometric assays of glucocorticoid receptors and heat shock proteins.

Our protein malnourished mice exhibit decreased resistance to infection with bacteria such as Listeria monocytogenesand Salmonella enteritidis, and by the fungus, Candida albicans. We have shown that corticosterone causes decreased killing of Candida by neutrophils in these mice in addition to slowing their ability to form abscesses, and we think this is due to diminution of T cell numbers below the level needed to produce the cytokines necessary to enhance host defenses. We have shown that the decreased resistance to Salmonella is due to a combination of low T cell numbers, which leads to diminished ability to synthesize enough interferon-gamma for efficient activation of macrophages, and direct inhibitory effects of corticosterone on macrophage activation. To gain more insight into the mechanisms by which these effects occur, we investigated the effects of corticosterone on macrophage synthesis/secretion of interleukin-12 (IL-12) and T cell synthesis/secretion of IL-4, IL-10 and interferon-gamma. These studies were facilitated by the use of cytokine analysis and flow cytometric quantification of T cell and macrophage phenotypes.

Selected Publications

  • Barone, K. Siobhan and John R. Stevenson. 1994. Characterization of Thymic Atrophy and Regeneration in Protein-Malnourished Weanling Mice. Journal of Nutritional Immunology, 3:13-26.
  • Barone, K. Siobhan, Patricia C. M. O'Brien, and John R. Stevenson.1993. Characterization and Mechanisms of Thymic Atrophy in Protein-Malnourished Mice: Role of Corticosterone. Cellular Immunology, 148:226-233.
  • Mellencamp, Mark W., Patricia C. M. O'Brien, and John R. Stevenson.1991. Pseudorabies Virus-Induced Suppression of MHC Class I Antigen Expression. Journal of Virology, 65:3365-3368.
  • Williams, Megan E., Donald C. Cox, and John R. Stevenson. 1986.Rejection of Reovirus-Treated L1210 Cells by Mice. Cancer Immunology and Immunotherapy, 23:87-92.