INHIBITION OF T CELLS BY TRYPTOPHAN DEGRADATION

Project: Research project

Project Details

Description

Description: Preliminary data from the applicant's lab suggests that
tryptopha is required for the proliferation, but not the activation of T
cells. The enzyme, indoleamine 2,3-dioxygenase (IDO), is produced by some
macrophages, an results in anergy of T cell which see antigen presented by
these macrophages. Using tryptophan deficient medium and anti CD3/CD28
activation, they will examine the biology of the T cell arrest. Initially
they will determine the cell cycle arrest point induced by tryptophan
starvation. They will examine RN for cell cycle control genes (CDK1, CDK4,
cyclin E, p21 p27) apotosis genes (fas, bcl2, bax, bak, bclx,) cytokines
IL2, IFN-g, IL2R), they will also examine the same proteins by western blot
as well. Cell surface phenotyping will be performed. They will determine
if CTL activity can be developed under tryp- culture. Again CD3/CD28
activation will be carried out and induction of perforin, granzyme and TNF
will be assessed. Finally they will test if already activated CTL can kill
macrophage targets. They will determine if energy induced is reversible,
and finally determine in HIV infected macrophages have IDO induced, and if
anergized T cell are present in HIV+ asymptomatic individuals.
StatusFinished
Effective start/end date9/30/989/29/01

ASJC

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