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Kathleen M. Gilbert
Associate Professor, Department of Microbiology & Immunology Immunology Research Interest: Cellular and molecular mechanisms of tolerance induction Ph.D ., Tulane University Postdoctoral, Sloan-Kettering Institute, NY, and The National Institute for Medical Research, London Phone: (501) 364-4587 Research Description Autoimmune diseases are primarily driven by the T cells of the immune system, and involve the activation of self-reactive T cells that are normally kept quiescent by the immune mechanism referred to as peripheral T cell tolerance. This mechanism clearly breaks down in the autoimmune state. Autoimmune diseases are most often treated with drugs that nonspecifically suppress all T cell function, and can lead to severe side effects. In an attempt to develop a better treatment for autoimmune disease we are studying a newly patented compound that appears to specifically inactivate only the self-reactive T cells involved in autoimmunity, and thereby restore a state of T cell tolerance to self-antigens. In order to promote the use of T cell tolerance induction as a method of immune intervention, we are studying the molecular mechanisms that mediate this event. This approach uses cloned mouse T cells, and concentrates on studying how one family of cellular proteins that regulate cell cycle, namely cyclin-dependent kinase inhibitors, interact with other signal transduction pathways that control T cell proliferation. Lastly, this laboratory is studying how different environmental toxicants found in the water supply promote autoimmune disease. This study uses MRL+/+ mice and studies the various immune system changes that occur when these mice are exposed to environmental chemicals. Mechanistic studies concerning how these chemicals promote T cell activation are also underway. References Blossom, S.J., Doss, J.C., and Gilbert K.M. 2006. Ability of Environmental Toxicant trichloroethylene to promote immune pathology is strain specific. in press. J. Immunotox. Blossom, S.J, Doss, J.C, Gilbert, K.M. 2006. Chronic exposure to a trichloroethylene metabolite in autoimmune-prone MRL+/+ mice promotes immune modulation and alopecia. Tox. Sci, Oct. 31; Epub ahead of print. Blossom, S.J., Gilbert, K.M. 2006. Exposure to an environmental toxicant, trichloroethylene, attenuates CD4 + T cell activation-induced cell death by metalloproteinase-dependent FasL shedding. Tox. Sci. July; 92 (1) 103-114. Blossom, S.J., Pumford, N.R., Gilbert, K.M. 2004. Activation and attenuation of apoptosis of CD4 + T cells following in vivo exposure to two common environmental toxicants, trichloroacetaldehyde hydrate and trichloroacetic acid. J. Autoimmun. Nov.; 23 (3) 211-20. Jackson, S.K., DeLoose, A., and Gilbert, K.M. 2001. Induction of anergy in Th1 cells associated with increased levels of cyclin-dependent kinase inhibitors p21 Cip1 and p27 Kip1 . J Immunol, 166: 952-958. Fan, M., Du, L., Stone, A.A., Gilbert, K.M., and Chambers, T.C. 2000. Modulation of MAP Kinases and Phosphorylation of Bcl-2 by Vinblastine Represent Persistent Forms of Normal Fluctuations at G 2 /M, Cancer Research , 60: 6403 – 6407. Griffin, J.M., Gilbert, K.M., Lamps, L.W. and Pumford, N.R. 2000. CD4+ T cell activation and induction of autoimune hepatitis following trichloroethylene treatment in MRL+/+ mice, Toxicological Sciences 57:345 – 352. Gilbert, K.M., Fetcher, N., Wahid, R. and Fifer, E.K. 2000. Potential clinical use of butyric acid derivatives to induce antigen-specific T cell inactivation, J. Pharmacol. Exp. Ther. 294:1146 – 1153. Blossom, S. and Gilbert, K.M. 2000. B cells from autoimmune BXSB mice are hyporesponsive to signals provided by CD4 + T cells. Immunol. Invest . 29:287- 297. Griffin, J.M., Gilbert, K.M., and Pumford, N.R. 2000. Inhibition of CYP2E1 reverses CD4 + T cell alterations in trichloroethylene-treated MRL+/+ mice. Toxicological Sciences 54:384-389. Griffin, J.M., Blossom, S.J., Jackson, S.K., Gilbert, K.M., and Pumford, N.R. 2000. Trichloroethylene accelerates an autoimmune response in association with Th1 T cell activation in MRL+/+ mice. Immunopharm 46:123-137. Drake, R.R., Wilbert, T.N., Hinds, T.A., and Gilbert, K.M. 1999. Differential ganciclovir-mediated cell killing by glutamine-125 mutants of herpes simplex virus type 1 thymidine kinase. J. Biol. Chem ., 274:37186-37192. Blossom, S. and Gilbert, K.M. 1999 . Antibody production in autoimmune BXSB mice. I. CD40L-expressing B cells need fewer signals for polyclonal antibody synthesis. Clin. Exp. Immunol. 118:147-153. Gilbert, K.M., Griffin, J.M., and Pumford, N.R. 1999. Trichloroethylene activates CD4 + T cells: potential role in an autoimmune response. Drug Metabolism Rev. 31:901-916. Blossom, S., E.B. Chu, W.P. Weigle, and K.M. Gilbert. 1997. CD40L expressed on B cells in the BXSB mouse model of systemic lupus erythematosus. J. Immunol. 159:4580-4588.
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