IL-4 INDEPENDENT IL-13 MEDIATED PROTECTIVE IMMUNITY

  • Gause, William (PI)
  • GAUSE, WILLIAM CLARK (PI)
  • GAUSE, WILLIAM CLARK (PI)
  • GAUSE, WILLIAM CLARK (PI)

Project Details

Description

Gastrointestinal nematodes of the genus Trichuris cause great
morbidity and increased susceptibility to infectious agents in humans. Immune
protection against Trichuris infection has been shown to be T cell-dependent
and associated with IgE elevations and mastocytosis. We have used the natural
murine parasite, Trichuris muris, as a model for understanding the development
of the protective response. In our studies, we have recently identified a
novelty pathway leading to worm expulsion in this parasite. Blocking T cell
costimulation, with the B7 antagonist, CTLA4lg, triggers immune deviation from
a host protective type 2 immune response characterized by elevations in IL-4
and IL-13 elevations. Additional blockade of IFN-gamma restores the host protective
response, although IL-4 levels remain inhibited. Further studies show that the
IL-4 independent protective response that can occur following IFN-gamma blockade is
IL-13 dependent, suggesting that IL-13 can mediate host protection in the
absence of a type 2 IL-4 dominant immune response. In these studies, we propose
to analyze the regulation of IL-13 expression and function following B7
blockade of the T. muris mucosal in vivo immune response addressing the
following specific aims: 1) identify the cell lineage that produces IL-13 when
B7 interactions and IL-4 production are blocked; 2) examine the differentiation
pathway leading to IL-13 production during the IFN-gamma dominant response; 3)
determine the mechanism of IFN-gamma modulation of IL-13 effector function.
StatusFinished
Effective start/end date3/15/002/28/06

Funding

  • National Institute of Allergy and Infectious Diseases: $266,016.00

ASJC

  • Medicine(all)
  • Immunology and Microbiology(all)
  • Parasitology

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