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Dale S. Gregerson, Ph.D.
Professor
Department of Ophthalmology
University of British Columbia, 1976, Ph.D.
grege001@umn.edu
612-626-0772 - office
612-626-0773 - lab
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Research Interests:
Autoimmunity and Tolerance
A central problem in immunology is that the ability to generate
a large variety of antigen receptors also results in the production
of receptors with specificity for self. The potential for
self-reactivity is balanced by compensatory/regulatory mechanisms,
collectively called tolerance. Tolerance is an operational
definition which refers to the lack of, inhibition of, or
alteration of an immune response. There are several types
of tolerance including: clonal deletion, anergy, suppression,
and immunological ignorance (lack of sufficient antigen to
achieve levels of receptor binding required for signaling).
Some tolerance results from the "fail- safe" manner
in which the immune system operates; a minimum of two signals
between two cells is required for activation.
One way to study tolerance is to use examples of the loss
of tolerance such as autoimmune disease. Our lab works with
an autoimmune disease, experimental autoimmune uveoretinitis
(EAU), in which the target autoantigen is a protein expressed
in retinal photoreceptor cells. EAU resembles several clinical
diseases of the retina with possible autoimmune origins. Nervous
system autoantigens provide unique challenges to tolerance.
Some of these autoantigens are tissue-specific, no antigen
is available to drive negative selection in the thymus. Some
appear for the first time well after the immune system has
started to generate mature T lymphocytes, so that these lymphocytes
have escaped usual selective mechanisms. Furthermore, the
nervous system is isolated behind physiological barriers,
whose effect on immune function is not well understood.
Our lab concentrates on studies of the role of the nervous
system environment in immune tolerance. The projects look
directly at the consequences of tissue-specific antigen expression
on tolerance. Transgenic mice expressing bacterial beta-galactosidase
on a retina- specific promoter, or on other promoters directing
expression to other sites, are used to compare the effects
of retina-restricted expression to systemic or CNS expression
on tolerance. A beta-galactosidase-specific T cell receptor
transgenic mouse has been made to provide a clonal population
of naive T cells with specificity for this antigen.
Another project asks how cells in immune privileged tissues
have a direct effect on how lymphocytes are activated and
respond; for example, we found that corneal endothelial cells
block IL-2, IL-4 and IFN-g production, but not IL-5 or IL-6
production by T cells. We are using expression cloning as
a strategy to find and identify factors that mediate this
regulatory response.
Selected Recent Publications:
- Sam TN, Xiao J, Roehrich H, Low WC, Gregerson DS. 2006. Engrafted neural progenitor cells express a tissue-restricted reporter gene associated with differentiated retinal photoreceptor cells. Cell Transplant. 15(2):147-60.
- Ferrington DA, Tran TN, Lew KL, Van Remmen H, Gregerson DS. 2006. Different death stimuli evoke apoptosis via multiple pathways in retinal pigment epithelial cells. Exp Eye Res. 83(3):638-50.
- McPherson SW, Heuss ND, Roehrich H, Gregerson DS. 2006. Bystander killing of neurons by cytotoxic T cells specific for a glial antigen. Glia. 53(5):457-66.
- McPherson SW, Roberts JP, Gregerson DS. 2005. Peripheral expression of rod photoreceptor arrestin induces an epitope-specific, protective response against experimental autoimmune uveoretinitis. Curr Eye Res. 30(6):491-502.
- McPherson, S.W., Yang, J., Chan, C.-C., Dou, C. and Gregerson, D.S. 2003. Resting
CD8 T cells recognize b-galactosidase expressed in the immune privileged
retina, and mediate autoimmune disease when activated. Immunol. 110:386-396.
- Dinges, M.M., Gregerson, D.S., Tripp, T.J., McCormick,
J.K. and Schlievert,
P.M. 2002. Effects of total body irradiation and cyclosporin A
on the lethality of
toxic shock syndrome toxin-1 in rabbits. J.
Infect. Dis.188:1142-1145.
- Gregerson, D.S. and Xiao, J. 2001. Failure of memory (CD44
high) CD4 T cells to
recognize their target antigen in retina. J.
Neuroimmunol. 120:34-41.
- Mi, P., Kawashima, H. and Gregerson, D.S. 2000. Local regulation
of the immune
response. Corneal endothelial cells inhibit T cell activation
and cytokine
production. Cytokine,
12:253-264.
Last updated: October 24, 2006 |
