Ellen Kraig, Ph.D.Professor
Brandeis University, 1981
Dr. Kraig is primarily involved in teaching graduate courses. She received the UTHSCSA Presidential Award for Teaching Excellence in 1996, the Dean's Award for Exceptional Graduate Teaching in 2000, and was elected to the UT Academy of Health Science Educators in 2006.
Effects of aging on immunity and autoimmunity
It has been well documented that immunosenescence is associated with increased susceptibility to infection and cancer as well as with diminished vaccine efficacy in older individuals. Moreover, potentially pathogenic autoimmune responses increase with age.
Our lab is currently focusing on the differential regulation of effector T cells and regulatory cells (Tregs) during aging in order to develop therapies that could potentially enhance immunity and decrease autoimmunity in the elderly. We have focused on several different systems to address these questions, as follows:
- First, MG (myasthenia gravis) is an autoimmune disease characterized by antibodies directed at the acetylcholine receptor (AChR). We generated a novel transgenic model in which the a chain of the T-AChR molecule is expressed as a "self" protein so that tolerance mechanisms can be assessed. This model is also being used to study changes in immune regulation with aging. Specifically, we have demonstrated that regulatory T cells (Tregs) are required for the maintenance of tolerance to AChR and are maintained with aging.
- Second, in studies being undertaken in both murine and nonhuman primates, we have established that memory immunity survives aging. Moreover, we recently demonstrated that old baboons immunized with LcrV, a protein antigen from Y. pestis, the plague bacterium, show unexpectedly vigorous antibody responses. We are now immunizing other nonhuman primate (NHP) species to determine whether baboon is unique in its ability to evade immunosenescence and to measure the efficacy of memory immunity. These models will provide insights into appropriate NHPs to use in testing vaccines for immunizing elderly humans and to potential therapeutic approaches for enhancing humoral immunity in older individuals.
- Lastly, given our interest in immune aging, we were fascinated by a recent finding [Harrison et al. Nature (2009)] that an immunosuppressive drug, rapamycin, could increase longevity in mice, even when the treatment was initiated relatively late in life. Since older individuals have diminished immune competence, it seemed counter-intuitive that further assaults on their immune systems would be beneficial. Indeed, in pilot experiments, we discovered that rapamycin did suppress humoral (antibody) responses to some antigens and thus, might compromise the ability of a treated individual, particularly an older one, to respond appropriately to an immune challenge. The contribution of Tregs is being addressed in this model as well.
Stacy S, Williams EL, Standifer NE, Pasquali A, Krolick KA, Infante AJ, Kraig E. (2010) Maintenance of immune tolerance to a neo-self acetylcholine receptor antigen with aging: implications for late-onset autoimmunity.
J Immunol. 2010 Jun 1;184(11):6067-75. Epub 2010 Apr 30.
Williams, E., S. Stacy, A.J. Infante, and E. Kraig (2009) Chapter 13. Mechanisms of tolerance in experimental models of myasthenia gravis. In P. Christadoss (ed.), Myasthenia gravis (pp. 235-257).
Stacy S, Pasquali A, Sexton VL, Cantwell AM, Kraig E., Dube PH. (2008) An age-old paradigm challenged: old baboons generate vigorous humoral immune responses to LcrV, a plague antigen. J Immunol. 2008 Jul 1;181(1):109-15. (Figure below).
Standifer NE, Stacy S, Kraig E, Infante AJ. (2007) Discrete T cell populations with specificity for a neo-self-antigen bear distinct imprints of tolerance. J Immunol. 2007 Mar 15;178(6):3544-50.
Stacy S, Infante AJ, Wall KA, Krolick K, Kraig E. (2003) Recall immune memory: a new tool for generating late onset autoimmune myasthenia gravis. Mech Ageing Dev. 2003 Aug-Sep;124(8-9):931-40.
Stacy S, Gelb BE, Koop BA, Windle JJ, Wall KA, Krolick KA, Infante AJ, Kraig E. (2002) Split tolerance in a novel transgenic model of autoimmune myasthenia gravis. J Immunol. 2002 Dec 1;169(11):6570-9.
Effects of age on the antibody response to LcrV in baboons and mice. (These data have been published in Journal of Immunology 181:109-115)