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Research Interests
Self versus non-self discrimination is one of the basic tenets of immunology.
Our laboratory focuses on understanding how this self "tolerance"
(or unresponsiveness) is learned by both B cells and T cells in normal
and in transgenic mice. For example, we have expressed model epitopes
(as IgG fusion proteins) in retroviral vectors for infection of lymphoid
precursors and the induction of tolerance. This is also being applied
to modulation of diabetogenic peptides, myelin basic protein in MS, anti-FVIII
inhibitors, to eliminate potentially harmful humoral responses in HIV
infection, and has obvious ramifications a variety of autoimmune disorders
including uveitis and for gene therapy in general. Moreover, if coupled
with co-stimulatory products, this approach may be utilized on augmenting
immune responsiveness in cancer patients. In addition, we have been examining
the regulation of growth and apoptosis in a unique group of B-lymphoma
lines, whose proliferation can be inhibited by the cross-linking of immunoglobulin
(IgM) receptors with anti-IgM. This process leads to inactivation of a
cyclin:cdk kinase complex, upregulation of a kinase inhibitor (p27) and
then apoptosis. Understanding the role of oncogenes and of Fas signaling
in tumorigenesis is an important goal.
Selected Publications Top
Scott, D.W., Grdina, T. and Shi, Y. 1996. T cells commit suicide but B cells are murdered. J. Immunology, 156: 2352.
Carey, G. and Scott, D.W. 2000. Role of PI3K in anti-IgM and anti-IgD
induced apoptosis in B-cell lymphomas. J. Immunol. 166: 1618-1626.
Agarwal, R. K., Kang, Y., Zambidis, E., Scott, D.W., Chan, C. and Caspi,
R.R. 2000. Retroviral gene transfer of an immunoglobulin-antigen fusion
protein protects from autoimmune disease. J. Clin. Invest., 106: 245.
Qian, J., Burkly, J., Smith, E.P., Ferrant, J.L., Hoyer, L., Scott, D.W.,
and Haudenschild, C.C. 2000. Role of CD154 in the secondary immune response:
the reduction of pre-existing splenic GC and anti-factor VIII inhibitor
titer, Eur. J. Immunol. 30: 2548-54.
El-Amine, M., Melo, M.E., and Scott, D.W. 2001. Gene therapy for tolerance
and autoimmunity: soon to be fulfilled promises? J. Clin. Immunol. 99:
1-6.
Contact Information Top
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