Cancer Institute A national cancer institute
designated cancer center

C. Garrison Fathman

Publication Details

  • Differential mTOR and ERK pathway utilization by effector CD4 T cells suggests combinatorial drug therapy of arthritis CLINICAL IMMUNOLOGY Lin, J. T., Stein, E. A., Wong, M. T., Kalpathy, K. J., Su, L. L., Utz, P. J., Robinson, W. H., Fathnnan, C. G. 2012; 142 (2): 127-138

    Abstract:

    The signaling pathways utilized by naïve and experienced effector CD4 T cells during activation and proliferation were evaluated. While inhibition of either mTOR or MAPK alone was able to inhibit naïve T cell proliferation, both mTOR and MAPK (ERK) pathway inhibition was required to efficiently block experienced, effector CD4 T cell proliferation. This was demonstrated both in vitro, and in vivo by treating mice with collagen-induced arthritis using mTOR and/or ERK inhibitors. The combination of mTOR and ERK inhibition prevented or treated disease more efficiently than either agent alone. These data illustrate the different requirements of naïve and experienced effector CD4 T cells in the use of the mTOR and MAPK pathways in proliferation, and suggest that therapies targeting both the mTOR and MAPK pathways may be more effective than targeting either pathway alone in the treatment of CD4 T cell-mediated autoimmunity.

    View details for DOI 10.1016/j.clim.2011.09.008

    View details for Web of Science ID 000300388200007

    View details for PubMedID 22075384

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