Research Interests:

Immunologic Tolerance, autoimmunity, mucosal immunopathology.

Basic Immunology texts teach that the central and peripheral tolerance mechanisms ensure that self-reactive T cells are purged from the T cell repertoire. However, it is clear that this view is overly simplistic. Interactions of T cells with self-ligands are critical for their peripheral homeostasis and reactivity toward foreign antigens. Furthermore, suppressor T cells, e.g., CD25+CD4 T cells, appear to defy negative selection and be specific for self-antigens. In addition, the very notion of “self” is somewhat difficult to define if one considers continuous exposure of the immune system to enteric and skin flora. We are probing these questions in the laboratory by dissecting the behavior of T cell directly in vivo. The dominant themes in the laboratory include:

• Mechanisms of suppression mediated by regulatory CD25+CD4 T cells.
  
• Peripheral mechanisms that shape the T cell repertoire, especially following recovery from lymphopenic states.
  
• The roles of self-ligands in T cell reactivity toward foreign antigens.
  
• Mechanisms of tolerance toward enteric flora.
  

Although most of our work deals with systems involving model nominal antigens, we are very interested in autoimmunity. We are actively studying models of inflammatory bowel disease and have recently developed a novel murine model of atopic dermatitis.

Selected Recent Publications:

• Thorstenson KM, Herzovi L, Khoruts A. 2005. A model of suppression of the antigen-specific CD4 T cell response by regulatory CD25+CD4 T cells in vivo. Int Immunol. 17(4):335-42.

• Hagen KA, Moses CT, Drasler EF, Podetz-Pedersen KM, Jameson SC, Khoruts A. 2004. A role for CD28 in lymphopenia-induced proliferation of CD4 T cells. J Immunol. 173(6):3909-15.  

• Moses, C.T., K.M. Thorstenson, S.C. Jameson, and A. Khoruts. 2003. Competition for self ligands restrains homeostatic proliferation of naive CD4 T cells. Proc. Natl. Acad. Sci. USA. 100:1185-1190.

• Reinhardt, R.L., A. Khoruts, R. Merica, T. Zell, and M.K. Jenkins. 2001. Visualizing the generation of memory CD4 T cells in the whole body. Nature. 401:101-105.

• Thorstenson, K.M., and A. Khoruts. 2001. Generation of anergic and potentially immunoregulatory CD25+CD4+ T cells in vivo following induction of peripheral tolerance with intravenous or oral antigen. J. Immunol. 167:188-195.

Last modified on: October 24, 2006