Stebbing J, Portsmouth S, Kim U, Gotch F, Nelson M, Bower M, Patterson S, Gazzard B; IAS Conference on HIV Pathogenesis and Treatment (2nd : 2003 : Paris, France).
Antivir Ther. 2003; 8 (Suppl.1): abstract no. 922.
Chelsea and Westminster Hospital, London, UK
BACKGROUND: The diverse families of heat shock proteins (HSPs) bind antigenic peptides and play major roles in immune responses via their receptor, CD91. We investigated the role of this pathway in HIV-1 seropositive individuals with and without Kaposi's sarcoma. METHODS: Twelve patients with KS were matched for CD4 count and HIV-1 viral load to individuals without Kaposi's sarcoma. We compared the potentials of KS-DC for stimulating allogeneic T cells and investigated the pathways utilized by tumour lysates, viral lysates and viral particles in their activation. In particular, we observed immune activation following heat shock protein receptor blockade. Findings: Despite an impaired allostimulatory capacity, these dendritic cells can prime the adaptive arm of the immune system in a saturable fashion following exposure to a wide and diverse variety of antigens. Such priming with disease-associated antigens is shown to occur through CD91, the heat shock protein receptor leading to phenotypic activation and stimulation of tetramer positive CD8 positive cytotoxic T cells. Additionally, we show that interferon producing plasmacytoid DC are significantly reduced in number in KS positive compared to matched KS negative HIV-1 infected individuals. Interpretation: Infected and functionally impaired DC can cross prime immune responses via CD91. These results have important implications for the aetiopathogenesis of KS and for the development and design of any compounds including anti-tumour and anti-viral vaccines that are derived from cellular lysates.
Publication Types:
Keywords:
- Antigens
- Antigens, Bacterial
- Antigens, Surface
- CD4 Lymphocyte Count
- Case-Control Studies
- Dendritic Cells
- HIV-1
- Heat-Shock Proteins
- Histocompatibility Antigens
- Humans
- K antigens
- Sarcoma, Kaposi
- T-Lymphocytes
- immunology
Other ID:
UI: 102263200
From Meeting Abstracts