Dr. Thomas Forsthuber
Cellular immunology, T cell immunity, and autoimmune diseases:
The immune system plays a fundamental role in the defense against microbial pathogens. However, erroneous activation of the immune system can lead to autoimmune diseases. Our laboratory pursues several lines of investigation to understand how T cells contribute to autoimmune diseases and protection from infection, and how to modulate T cell immunity for therapeutic purposes in humans.
1) Autoimmune diseases: We have developed novel models to understand how T cells contribute to autoimmune diseases and how to stop “bad” T cells. We are studying experimental autoimmune encephalomyelitis (EAE, a mouse model for multiple sclerosis, MS), and collagen or human cartilage gp-39 induced arthritis (as a model for rheumatoid arthritis, RA) in “humanized” transgenic mice that express human genes such as transplantation antigens (MHC genes). Using this system we can address questions directly relevant for human patients and test novel treatments, which is otherwise not possible (Forsthuber, J. Immunology 2001; Gross, Science 1998; Klehmet, Clinical Immunology, 2004).
2) Vaccine development: We are interested in the development of new adjuvant formulations for human vaccines. We are in particular interested in pharmacological targeting of the signaling cascades which determine the induction of type-1/type-2 cytokine T cell responses, as is required to develop vaccines and therapies of autoimmunity. We have pioneered the cytokine ELISPOT assay as a mainstream method to measure T cell responses to antigens in animals and humans (Forsthuber, Science, 1996, Denkinger, Int. Immunopharmacology, 2004).
3) T cell biology: One of our current interests is the role of MAP kinases in T cell development and function. Moreover, we are studying the role of macrophage migration inhibitory factor in T cell development, function, and in autoimmunity. Finally, we are investigating neonatal T cell immunity (Nekrasova, J. Immunology, 2005; Forsthuber, Science, 1996; Denkinger, J. Immunology, 2003).
Cathi Murphey, Steve Chang, Bernard Arulanandam, and Thomas G. Forsthuber. Pertussis Toxin induces polyclonal CD8+ T cell activation, cytokine production, and killer function. Cellular Immunology, 267(1): 50-55 (2011). PMID: 21130421
Ji, N., Sosa, RA, and Forsthuber, TG. T-bet: more than just a “T-box”: its role as a possible biomarker and therapeutic target in autoimmune diseases. Immunotherapy, 3(3):435-441 (2011)
Li, W.; Murthy, A.K.; Guentzel, M.N.; Chambers, J.P.; Forsthuber, T.G.; Seshu, J.; Zhong, G.; Arulanandam, B.P. Immunization with a combination of integral chlamydia antigens and a defined secreted protein induces robust immunity against genital chlamydial challenge. Infect. Immun. Infect. Immun. 78(9): 3942-3949 (2010)
Cantor, J, Hyeon, Y, Dixit, A, Iverson, B, Forsthuber, TG, Georgiou, G. Therapeutic enzyme deimmunization by combinatorial T-cell epitope removal using neutral drift. PNAS,
108(4):1272-1277 (2011) PMID: 21209329; PMCID PMC3029727.
Ji, N., Rao, N., Guentzel, N.M., Arulanandam, B.P., and Forsthuber, T.G., Anaphylaxis and mortality induced by treatment of mice with anti-VLA-4 antibody and pertussis toxin. J. Immunol., 186(5):2750-2756 (2011) PMID:21270409.
Ashlesh Murthy, Weidang Li, Bharat Chaganty, Sangamithra Kamalakaran, M Guentzel, Janakiram Seshu, Thomas Forsthuber, Guangming Zhong, and Bernard Arulanandam. TNF-α Production from CD8+ T Cells Mediates Oviduct Pathological Sequelae Following Primary Genital Chlamydia muridarum Infection. Infect. Immun. 79:2928-2935 (2011).
Ji, Niannian, Day, Robert T., Mardale, A., and Forsthuber, Thomas G., Macrophage migration inhibitory factor promotes resistance to glucocorticoids in experimental autoimmune encephalomyelitis. Manuscript in preparation.
Ji, Niannian, and Forsthuber, Thomas G., The critical contribution of MIF produced by different inflammatory cell types in EAE. Manuscript in preparation.
Thathiah, P., Sanapala, S., Rodriquez, A.R., Yu, J.J., Murthy, A.K., Guentzel, M.N., Forsthuber, T.G., Chambers, J.P., Arulanandam, B.P. Non-FcepsilonR bearing mast cells secrete sufficient interleukin-4 to control Francisella tularensis replication within macrophages. Cytokine 55(2) 211-220 (2011)
Sosa, R.A., Forsthuber, T.G., The critical role of antigen-presentation-induced cytokine crosstalk in the central nervous system in multiple sclerosis and experimental autoimmune encephalomyelitis. J. Interferon Cytokine Res. 31(10)753-768 (2011)
Arellano B, Hussain R, Zacharias T, Yoon J, David C, Zein S, Steinman L, Forsthuber TG, Greenberg BM, Lambracht-Washington D, Ritchie AM, Bennett JL, Stüve O. Human aquaporin
4 281-300 is the immunodominant linear determinant in the context of HLA-DRB1*03:01 – Relevance for diagnosing and monitoring patients with neuromyelitis optica. Archives of Neurology. In press.