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BIOGRAPHY:
Dr. Heath is Senior Research Fellow in the Immunology/Health Department of the Walter and Eliza Hall Institute of Medical Research in Melbourne. He received his Ph.D. in 1988 in the field of immunology from the University of Melbourne in Australia. He did postdoctoral work in the United States in the Immunology Department of Scripps Research Institute. In 1993 he received an Australian Research Fellowship, and in 1998 was awarded the Burnet Prize from the Walter and Eliza Hall Institute. His HHMI-funded research concerns self tolerance and viral immunity.
RESEARCH ABSTRACT SUMMARY:
The Role of Cross-Presentation in Self Tolerance and Viral
Immunity
We have previously shown that mice expressing ovalbumin (OVA) in
their pancreatic islet beta cells induced the deletion of
CD8+T cells specific for this autoantigen. This
Bim-dependent deletion process involves cross-presentation of islet
antigens by a CD8+ subset of dendritic cells, which appear
to scan all tissues for self-antigens. In an attempt to understand the
need for such a peripheral surveillance system, we investigated the
role of dendritic cell subsets in viral immunity. This work revealed
that the same subset of CD8+ dendritic cells was heavily
involved in the generation of cytotoxic T cell immunity to three
different viral infections: herpes simplex virus type 1, influenza
virus, and vaccinia virus. Given that CD8+ dendritic cells
are the major subset responsible for cross-presentation of cellular
antigens, our data suggest that they form a surveillance network that
captures cell-associated antigens from peripheral tissues and, in the
absence of infection, induces tolerance, but during viral infection is
responsible for cross-priming cytotoxic T cell immunity. Examination of
the mechanism by which the CD8+ dendritic cells obtain viral
antigen suggests that this lymph node–resident subset may require the
participation of other dendritic cells for the trafficking of viral
antigens from the site of infection to the draining node.
Photo: Kent Kallberg, Kallberg Studios
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