The Immunology Core primarily provides support for Project 1 and Project 3. For these projects, pigtail macaques will be infected with SHIV, with some then receiving various treatments intended to control viral replication and influence the viral reservoir. The Core will longitudinally measure the SHIV-specific CD4+ and CD8+ T cells in the blood of these animals at different stages in the treatment regimens. These measurements will be made using a flow cytometric intracellular cytokine staining (ICS) assay. For this assay, peripheral blood mononuclear cells (PBMC) are stimulated ex vivo for 6 hours with pools of overlapping 15-mer peptides that match the sequence of the HIV/SIV proteins encoded by the virus used to infect the monkeys. Depending on the amount of PBMC available at each time point, responses to all SHIV-encoded proteins or only selected proteins will be examined. This is a multi-parametric assay that measures multiple cytokines as well as memory markers;therefore, we can measure both the magnitude and the character or quality of the response. Many groups have published reports proposing associations between effective or non-effective T-cell responses and particular functional or phenotypic profiles. Thus, a detailed characterization of the T-cell responses that are gained or lost subsequent to the treatment interventions in these projects will be informative for correlating with treatment outcome.

Public Health Relevance

These projects will study treatment modalities aimed at decreasing the HIV reservoir. The Immunology Core will determine the effect of these treatments on the immune system, particularly the T-cell component. This is useful not only for monitoring the effectiveness of these treatments, but also for describing the type of T-cell response that may be useful to diagnostically monitor HIV disease and treatment.

Agency
National Institute of Health (NIH)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19AI096111-04
Application #
8691712
Study Section
Special Emphasis Panel (ZAI1)
Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Fred Hutchinson Cancer Research Center
Department
Type
DUNS #
City
Seattle
State
WA
Country
United States
Zip Code
98109
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