This is a new R29 submission to study the roles of co-stimulatory molecules B7.1 and B7.2, as well as cytokines IL4 and IL10, in the regulation of CTL activity toward HIV. The proposal is based on a series of observations, which illustrate that while vigorous CTL responses to HIV are detected in acute and chronically infected subjects, they are unable to completely inhibit virus replication and eradicate disease. The hypothesis advanced is that CTL to HIV may be suppressed in early to mid stage disease due to the lack of co-stimulatory molecule B7.1 expression in lymphoid germinal centers. The lack of B7.1 engagement of CTL is proposed to result in enhanced production of IL4, which fosters an environment where naive CD8+ cells are unable to develop into functional/activated CTL. There are three specific aims: (1) to quantitative t he expression of B7.1 and B7.2, and the production of IL4 and IL10 in lymph node germinal centers at various stages of HIV infection; (2) to determine the effect of HIV replication on the expression of co-stimulatory molecules and cytokine production; and (3) to investigate the relationship between co-stimulatory molecule expression, cytokine production and CTL function in vitro.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29AI042499-03
Application #
6137247
Study Section
AIDS and Related Research Study Section 1 (ARRA)
Program Officer
Plaeger, Susan F
Project Start
1998-01-01
Project End
2002-12-31
Budget Start
2000-01-01
Budget End
2000-12-31
Support Year
3
Fiscal Year
2000
Total Cost
$105,088
Indirect Cost
Name
University of Colorado Denver
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
065391526
City
Aurora
State
CO
Country
United States
Zip Code
80045
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