Research Interests

Immunology

Some of the most fascinating, complex and relevant problems in biology involve the interplay of separate physiological systems, and the effects of these interactions on the whole animal. We have concentrated on genetic and environmental factors which influence the normal immune response, with the goal of defining key triggers for immune response regulation. Currently, we are investigating the role of growth hormone (GH) on immune response control. Evidence accumulated from many sources indicates that the immune response is influenced by pituitary hormones, particularly GH. We are dissecting the effects of GH on the immune system by studying several aspects of the immune response in mice which overexpress or underexpress GH. The overexpressers are GH transgenic mice: they express extraordinarily high levels of GH throughout their lives. The excess GH effects many physiological systems, leading to dramatically larger size and reduced life span. Differences in overall immune responses, such as changes in the T cell response to mitogens, have also been documented. We are also studying the effects of underexpression of growth hormone on the immune response, using a genetic dwarf strain of mice which produces almost no GH.

At the molecular level, we have investigated the immune response in by looking at certain aspects of the T-cell lymphocyte repertoire in the GH transgenic and dwarf mice. We found that the relative number of splenic T cells, as compared to other nucleated cells, was significantly reduced in the GH transgenic mice. At a more specific level, we showed that a certain T-cell family, Vbeta8, was significantly increased in the transgenic animals. This gene family comprises up to 30% of the total T cells in some mice, and enhanced Vbeta8 expression may be linked to the onset of autoimmunity in the transgenic mice. Next, we examined T-cell receptor Vbeta chain sequence diversity, concentrating on the variable-diversity-joining gene segment junctional areas. We found that V-D-J diversity in both transgenic and normal mice is quite similar, indicating that basic T-cell receptor developmental patterns are not effected in the transgenic mice.

We are now looking for immune response differences between the transgenic, normal, and dwarf mice using an immune response to a model antigen, tetanus toxoid. The transgenic animals exhibit a reduced response to tetanus toxoid compared to the dwarf animals. Our next problem is to investigate the precise role of GH in the suppressed immune response of the transgenic animals.

Publications:

Meliska, C. J., Stunkard, M. E., Gilbert, D. G., Jensen, R. A., and Martinko, J. M. Immune function in cigarette smokers who quit smoking for 31 days. J. Allergy and Clinical Immunol. 95: 901-910, 1995.

Smith, W. C., Martinko, J. M., Wheeler, J. N., Hargrave, P. A., and McDowell, J. H. The deduced amino acid sequences of rabbit rod photoreceptor opsin. Gene 162: 331-332, 1995.

Gilbert, D. G., Stunkard, M. E., Jensen, R. A., Detwiler, F. R. J., and Martinko, J. M. Effects of exam stress on mood, cortisol, and immune functioning: influences of neuroticism and smoker--non-smoker status. Person. Individ. Diff. 21: 235-246, 1996.

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Department of Microbiology e-mail: microbiology@micro.siu.edu
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