US 5,843,635 AGranted

Inhibition of APC-mediated apoptosis of activated T lymphocytes

AssigneeDana-Farber Cancer Institute, Inc.

InventorsStuart F. Schlossman, Mei X. Wu

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Abstract

Methods for interfering with antigen presenting cell-mediated priming of resting peripheral blood T lymphocytes to undergo activation induced cell death ("apoptosis") by inhibiting an interaction between a membrane associated molecule ("an APC apoptotic ligand") present on stimulated antigen presenting cells ("APC") and a counter-receptor that is present on T lymphocytes are disclosed. The antigen presenting cells are preferably from the monocyte/macrophage cell line or are dendritic cells. Also disclosed are methods of screening for inhibitors of APC-mediated priming of T lymphocytes to undergo apoptosis and methods and agents for detecting, identifying and characterizing an APC apoptotic ligand. Inhibitors identified by the screening method of the invention are used to reduce the T lymphocyte depletion associated with HIV infection and thereby mitigate the severe immunodeficiency associated with AIDS by interfering with the association between HIV-infected antigen presenting cells, especially monocytes and macrophages, and T cells.

Claims8

Dependent claims

A method of screening for an inhibitor of antigen presenting cell-mediated priming of resting peripheral blood T lymphocytes to undergo activation induced apoptosis, said method comprising the steps of:

providing first and second samples of components for a T lymphocyte apoptosis assay, said components comprising resting peripheral blood T lymphocytes and stimulated antigen presenting cells selected from the group consisting of monocytes, macrophages and dendritic cells, said stimulated antigen presenting cells being provided for priming said T lymphocytes to undergo apoptosis;
causing said first sample of components to react in said apoptosis assay, wherein the extent of T lymphocyte apoptosis in said first assay sample is determined;
adding a candidate inhibitor to said second sample of components;
causing said second sample of components containing said candidate inhibitor to react in said apoptosis assay, wherein the extent of T lymphocyte apoptosis in said second assay sample is determined;
and
comparing said extent of T lymphocyte apoptosis in said first assay sample to said extent of T lymphocyte apoptosis in said second assay sample to determine the effect of said candidate inhibitor.

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