Direct visualization of HIV-1-specific cytotoxic T lymphocytes during primary 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.
Wilson
J D
JD
Human Immunology Unit, Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford, UK.
Ogg
G S
GS
Allen
R L
RL
Davis
C
C
Shaunak
S
S
Downie
J
J
Dyer
W
W
Workman
C
C
Sullivan
S
S
McMichael
A J
AJ
Rowland-Jones
S L
SL
D000328:Adult; D000595:Amino Acid Sequence; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005434:Flow Cytometry; D015683:Gene Products, gag / Q000276:immunology; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D008297:Male
D015683:Gene Products, gag