Weak anti-HIV CD8+ T-cell effector activity in HIV primary infection
Marc Dalod, … , Martine Sinet, Alain Venet
Marc Dalod, … , Martine Sinet, Alain Venet
Published November 15, 1999
Citation Information: J Clin Invest. 1999;104(10):1431-1439. https://doi.org/10.1172/JCI7162.
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Article

Weak anti-HIV CD8+ T-cell effector activity in HIV primary infection

Abstract

HIV-specific CD8+ T cells play a major role in the control of virus during HIV primary infection (PI) but do not completely prevent viral replication. We used IFN-γ enzyme-linked immunospot assay and intracellular staining to characterize the ex vivo CD8+ T-cell responses to a large variety of HIV epitopic peptides in 24 subjects with early HIV PI. We observed HIV-specific responses in 71% of subjects. Gag and Nef peptides were more frequently recognized than Env and Pol peptides. The number of peptides recognized was low (median 2, range 0–6). In contrast, a much broader response was observed in 30 asymptomatic subjects with chronic infection: all were responders with a median of 5 peptides recognized (range 1–13). The frequency of HIV-specific CD8+ T cells among PBMC for a given peptide was of the same order of magnitude in both groups. The proportion of HIV-specific CD8+CD28– terminally differentiated T cells was much lower in PI than at the chronic stage of infection. The weakness of the immune response during HIV PI could partially account for the failure to control HIV. These findings have potential importance for defining immunotherapeutic strategies and establishing the goals for effective vaccination.

Authors

Marc Dalod, Marion Dupuis, Jean-Christophe Deschemin, Cécile Goujard, Christiane Deveau, Laurence Meyer, Nicole Ngo, Christine Rouzioux, Jean-Gérard Guillet, Jean-François Delfraissy, Martine Sinet, Alain Venet

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Comparison of the proportion of CD8+CD28+ T cells specific for HIV or ot...
Comparison of the proportion of CD8+CD28+ T cells specific for HIV or other viral peptides among CD8+ T cells. (a) Representative experiments from 3 HLA-B8–expressing individuals where PBMC were incubated in medium alone or stimulated with peptides EBNA-3 325-333 derived from EBV and Gag 259-267 from HIV-1. IFN-γ intracellular production (x axis) and CD28 expression (y axis) were analyzed on gated CD8+ T lymphocytes. 200,000 events were acquired for subject KJA and 400,000 for the other individuals. Absolute numbers of events are indicated in the right quadrants of each dot-plot. (b) Boxes representing the fraction of CD8+ CD28+ T cells (25th–75th percentile) specific for HIV peptides (gray boxes) or for influenza or EBV peptides (white boxes) in subjects with PI (n = 14) or chronic HIV infection (n = 14), and seronegative controls (n = 4).