The Mathis/Benoist laboratory works in the fields of Autoimmunity and T cell differentiation, with a special emphasis on exploiting the most advanced transgenic and gene-targeting technology to engineer new mouse models. Studies on Autoimmunity explore the immunological mechanisms underlying diabetes, rheumatoid arthritis and the polyendocrine disorder, APECED (or APS-1). Major questions tackled are what initiates these diseases, how is their progression regulated, and what are the final effector mechanisms. Modern genetic and genomic approaches are used to identify disease-modifying genes. Studies on diabetes and arthritis in humans include genetic analyses aimed at elucidating mechanisms and the development of genetic, cellular imaging and whole-organism imaging methods to improve disease prediction and to permit monitoring of responses to therapeutic intervention. Studies on T cell differentiation focus on: 1) selection of the T cell repertoire, in particular mechanisms of positive and negative selection and lineage commitment; and 2) cellular and molecular influences on naive T cell survival in the periphery.

Selected publications:

Diabetes

- J. Katz, B. Wang, K. Haskins, C. Benoist, D. Mathis: Following a diabetogenic T cell from genesis through pathogenesis. Cell (1993) 74,1089-1100.
- J. Katz, C. Benoist, D. Mathis: T helper cell subsets in insulin-dependent diabetes. Science (1995)
268,1185-1188.
- A. Gonzalez, J.D. Katz, M-G. Mattei, H. Kikutani, C. Benoist, D. Mathis: Genetic control of diabetes progression. Immunity (1997) 7,873-883.
- F. Leuhder, C. Chambers, J.P. Allison, C. Benoist, D. Mathis: Pinpointing when CTLA-4 must be engaged to dampen diabetogenic T cells. Proc. Natl. Acad. Sci. (USA) (2000) 97,12204-9.
- A. Gonzalez, I. Andre-Schmutz, C. Carnaud, D. Mathis, C. Benoist: Damage control, rather than unresponsiveness, effected by protective DX5+ T cells in autoimmune diabetes. Nature Immunol. (2001) 7,1117-1125.

Arthritis

- V. Kouskoff, A-S. Korganow, V. Duchatelle, C. Degott, C. Benoist, D. Mathis: Organ-specific disease provoked by systemic autoreactivity. Cell (1996) 87, 811-822.
- A.S. Korganow, J. Hong, S. Mangialaio, V. Duchatelle, R. Pelanda, T. Martin, C. Degott, H. Kikutani, K. Rajewsky, J-L. Pasquali, C. Benoist, D. Mathis: From systemic T cell self-reactivity to organ-specific autoimmune disease via immunoglobulins. Immunity (1999) 10,451-461.
- I. Matsumoto, A. Staub, C. Benoist, D. Mathis: Arthritis provoked by linked T and B cell recognition of a glycolytic enzyme. Science (1999) 286, 1732-1735.
- H. Ji, K. Ohmura, U. Mahmood, D.M. Lee, F.M.A. Hofhuis, S.A. Boackle, V.M. Holers, M. Walport, C. Gerard, A. Ezekowitz, M.C. Carroll, M. Brenner, R. Weissleder, J.S. Verbeek, V. Duchatelle, C. Degott, C. Benoist, D. Mathis: Arthritis critically dependent on innate immune system players. Immunity (2002) 16, 157-168.
- I. Matsumoto, M. Maccioni, D.M. Lee, M. Maurice, B. Simmons, M. Brenner, D. Mathis, C. Benoist: How antibodies to a ubiquitous cytoplasmic enzyme may provoke joint-specific autoimmune disease. Nature Immunol. (2002) 3, 360-365.

T cell differentiation

- N. Nakano, R. Rooke, C. Benoist, D. Mathis: Positive selection of T cells induced by viral delivery
of neopeptides to the thymus. Science (1997) 275, 678-683.
- R. Rooke, C. Waltzinger, C. Benoist, D. Mathis: Targeted complementation of MHC class II deficiency by intrathymic delivery of recombinant adenovirus. Immunity (1997) 7, 123-134.
- M. Correia-Neves, C. Waltzinger, D. Mathis, C. Benoist: The shaping of the T cell
repertoire. Immunity (2001) 14, 21-32.
- N. Labrecque, L.S. Whitfield, R. Obst, C. Waltzinger, C. Benoist, D. Mathis: How
much TCR does a T cell need? Immunity (2001) 15, 17-82.

Biographical sketch

Dr. Mathis is co-Head of the Section on Immunology and Immunogenetics at Joslin Diabetes Center and Professor of Medicine at Harvard Medical School. She obtained a BSc in Biology from Wake Forest University and a PhD in Biology from the University of Rochester. She performed postdoctoral studies at the Laboratoire de Genetique Moleculaire des Eucaryotes (LGME) in Strasbourg, France and at Stanford University Medical Center. She returned to France at the end of 1983, establishing a laboratory in conjunction with Dr. Christophe Benoist at the LGME (later IGBMC) in Strasbourg. The lab moved to the Joslin Diabetes Center at the end of 1999. Dr. Mathis is also an active member of the Program on Immunology at Harvard Medical School www.hms.harvard.edu/dms/immunology, the JDRF Center for Islet Transplantation at Harvard www.jdf-hms-islets.org and the Dana Farber/Harvard Cancer Center www.dfhcc.harvard.edu.