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A Technique to Simultaneously Visualize Virus-Specific CD8+ T Cells and Virus-Infected Cells In situ
Published on: August 13, 2009
Direct visualization of HIV-1-specific cytotoxic T lymphocytes during primary infection
J D Wilson1, G S Ogg, R L Allen
1Human Immunology Unit, Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford, UK.
Insights
Cytotoxic T lymphocytes (CTL) are crucial for controlling HIV-1. This study reveals significantly higher HIV-specific CD8 T cell frequencies in early infection than previously thought, directly correlating with viral load.
Area of Science:
- Immunology
- Virology
- Infectious Diseases
Background:
- Cytotoxic T lymphocytes (CTL) are vital for controlling HIV-1 replication.
- Previous methods likely underestimated HIV-specific CTL precursor frequency during primary infection.
Purpose of the Study:
- To quantify HIV-specific CD8 T cells in primary HIV infection using a novel technique.
- To investigate the dynamics and frequency of these cells in relation to viral load.
Main Methods:
- Utilized soluble tetrameric complexes of HLA class I molecules with HIV epitope peptides.
- Studied three patients with a focused HIV-specific CTL response during early HIV infection.
Main Results:
- HIV-1-specific CD8 T cell frequencies in acute infection are higher than previously reported.
- These responses are detectable before full seroconversion.
- Confirmed immunodominance of B27-restricted responses and a link between CD8 T cell numbers and viral load.
Conclusions:
- HIV-1-specific CD8 T cells respond to viral replication and aid in controlling early infection.
- Immunodominance of CD8 T-cell responses is established during the acute phase of HIV infection.
Objective:
HIV-specific cytotoxic T lymphocytes (CTL) are believed to play an important role in containing viral replication throughout HIV-1 infection. Previous studies have attempted to quantify the HIV-1-specific CTL precursor frequency during primary HIV infection by using limiting dilution analysis, which almost certainly underestimates the true CTL frequency. Here we use a relatively new technique to quantify HIV-specific CD8 T cells in primary HIV infection.
Methods:
We have used soluble tetrameric complexes of HLA class I molecules complexed with HIV epitope peptides to study the dynamics and frequency of HIV-specific CD8 T cells in relation to plasma viral load in early HIV infection, in three patients with a highly focused HIV-specific CTL response.
Results:
We show that the frequencies of HIV-1-specific CD8 T cells in acute infection are significantly higher than previously documented and can be demonstrated well before full seroconversion. These studies also confirm the immunodominance of the B27-restricted response in HIV infection and demonstrate a close temporal relationship between the numbers of circulating HIV-specific CD8 T cells and viral load.
Conclusions:
These findings strongly suggest that HIV-1-specific CD8 T cells are responding directly to the level of viral replication in early HIV infection and are a major factor in its control. In addition, the data indicate that immunodominance for CD8 T-cell responses is established in the acute phase of HIV infection.
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