joan wither
Joan WitherMD, PhD
Professor

Contact Info

T. (416) 603-6205

Location

University Health Network
Toronto Western Hospital
399 Bathurst Street
Toronto
ON, M5T2S8

Research Interests

Adaptive Immunity, Autoimmunity, Lupus

Accepting

Grad Students Must First Apply Through Department

The laboratory has two areas of interest. One set of studies focuses on the pathogenesis of Systemic Lupus Erythematosus (SLE) a multisystem autoimmune disease characterized by the development of autoantibodies to a variety of cellular constituents. Our investigations are centered on the NZB mouse as a model for this disease. Although the B cells in these mice are polyclonally activated previous work suggests that T cell help is required for the development of the high affinity pathogenic antibodies that mediate disease. To determine whether this T cell help arises from a generalized defect in T cell tolerance induction or an abnormality in T-B collaboration we have examined antigen-specific tolerance in beef insulin (BI) transgenic NZB backcross mice or following administration of aqueous protein antigens. Our studies show that in control BALB/c mice both the BI transgene and administration of aqueous BI induce a state of partial tolerance manifested by relative preservation of a Th2-like response with production of IgG1 BI-specific antibody but a marked reduction in Th1-associated IgG2a and corresponding IL-2 production. In contrast, NZB mice produce both isotypes of antibodies despite appropriate reduction of antigen-induced IL-2 production in response to tolerization. Further studies will focus on this altered response to tolerization. In particular, we will examine events occuring during T-B collaboration using adoptive transfer experiments, administration of cytokines and/or anti-cytokine mAbs and additional transgenic mouse model systems.

The other area of interest in the laboratory is the structure of the T cell recognition complex. We have previously generated several panels of BI-specific Ad-restricted T cell hybridomas bearing TCR chains that demonstrate limited amino acid differences in their alpha- or beta-chain V regions. To study the nature of the interaction between these TCR and the antigen/MHC complex we have systematically mutated the Ad molecule and are examining the ability of transfectants to present BI to our T cell hybridomas.

Publications and Awards

Recent Publications

  1. Wither, J., Pawling, J., Phillips, L., Delovitch, T., & Hozumi, N. J. Immunol. 146, 3513-3522 (1991).
  2. Wither, J., Poplonski, L., Delovitch, T., & Hozumi, N. Arthritis and Rheumatism 36, S93 (1993).
  3. Wither, J., Poplonski, L., & Vukusic, B. Arthritis and Rheumatism 37, R39 (1994).
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