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Immune
Activation,Tolerance, and Memory
Our research focuses on the control of immune activation, tolerance and
autoimmunity. In one project, the laboratory is using antigen receptor
transgenic mice in which selected immunoregulatory genes have been knocked
out to analyze the genetic basis of autoimmune disease. The particular
emphasis is on identifying genes that control tolerance and autoimmunity
to a transgene-encoded islet antigen, as a model of type I diabetes, and
to serum antigen as a model of systemic autoimmunity. The disease-associated
genes that are being studied are Fas and Fas ligand, IL-2, which is a
T cell growth factor and a potentiator of Fas-mediated apoptosis, and
CTLA-4, an inhibitor of T cell function. The second project focuses on
the biochemical mechanisms and physiologic significance of apoptosis in
lymphocytes. The third project deals with the external signals and biochemical
mechanisms that induce the differentiation of CD4 T lymphocytes into effector
and memory cells. The biochemical signals downstream of CD28 are being
defined by a mutational and gene complementation approach, in which CD28
mutants and putative signaling molecules are introduced into CD28- T cells
by retrovirus-mediated gene transfer. The mechanisms of memory cell generation
and survival are being studied in a TCR transgenic model.
Selected Publications:
Van Parijs L, and Abbas AK. Homeostasis and self tolerance in the immune
system: turning lymphocytes off. Science 1998; 280:243-248.
Abbas, AK and Janeway CA. Immunology: improving on nature in the twenty-first
century. Cell 2000; 100:129-138.
Kane LP, Andres PG, Howland KC, Abbas AK and Weiss A. Akt, acting through
the RE/AP element, provides the CD28 costimulatory signal for upregulation
of IL-2 but not Th2 cytokines. Nature Immunology 2001; 2:37-44
Contact Information:
Email: aabbas@itsa.ucsf.edu
Phone: 415/ 514-068
Address: Box 0506, Room M 590
The University of California, San Francisco, CA 94143, (415) 476-9000
Copyright 2003, The Regents of the University of California.
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