Immunity to HIV infection includes both cellular and humoral mechanisms. Dendritic cells (DCs) are good candidates to elicit HIV-specific immunity but optimal means to use them are not established. Three significant variables are i) the specific DC subset involved, 2) the antigens (Ags) used, and iii) the route of Ag acquisition by DCs. There are 3 well-characterized DC subsets identified in humans: Langerhans, interstitial, and lymphoid DCs. Several studies show that DCs elicit HIV-specific cellular immunity, but only studied monocyte-derived DCs. Ag formulation (apoptotic vs. necrotic) and acquisition pathway also influence elicited immunity, although little systematic study has been reported. A novel DC type, the macrophage (M)-derived DC, may have advantages over other DC subsets in eliciting HIV-specific immunity. The goal is to determine which DC subsets, acquiring Ag in specific contexts, elicit immune effector cells thought to be important in preventing HIV infection, and in controlling HIV replication. The focus on induction of cellular immunity because of the investigators expertise in that area. The hypothesize is that if optimal DC subsets and Ag acquisition pathways are identified in vitro, then ultimately specific targeting strategies may be used to make a convenient vaccine preparation that does not require the ex vivo growth or manipulation of autologous DCs. There are 3 specific aims: #1: to determine the differential ability of 3 DC subsets, interstitial or epidermal DCs derived from CD34+ HPCs and DCs produced from M-CSF derived Macrophages to activate HIV gag, pol, env or nef-specific T cells when Ags are acquired in two distinct contexts (endogenous production or exogenous capture). #2: to determine whether the specific effector cells elicited are those thought to prevent HIV infection, examining cytotoxicity, and cytokine/chemokine production (THl/TH2 and TCl/TC2 immunity); and #3: to determine the non-cytolytic capacity of these elicited immune cells to inhibit HIV

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21AI044322-01A1
Application #
6077841
Study Section
Special Emphasis Panel (ZRG1-VACC (03))
Program Officer
Bradac, James A
Project Start
2000-05-01
Project End
2002-04-30
Budget Start
2000-05-01
Budget End
2001-04-30
Support Year
1
Fiscal Year
2000
Total Cost
$257,957
Indirect Cost
Name
Baylor Research Institute
Department
Type
DUNS #
145745022
City
Dallas
State
TX
Country
United States
Zip Code
75204
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