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. 2005 Dec;79(23):14986-91.
doi: 10.1128/JVI.79.23.14986-14991.2005.

Tat(28-35)SL8-specific CD8+ T lymphocytes are more effective than Gag(181-189)CM9-specific CD8+ T lymphocytes at suppressing simian immunodeficiency virus replication in a functional in vitro assay

John T Loffredo  1 , Eva G Rakasz, Juan Pablo Giraldo, Sean P Spencer, Kelly K Grafton, Sarah R Martin, Gnankang Napoé, Levi J Yant, Nancy A Wilson, David I Watkins
Affiliations

Tat(28-35)SL8-specific CD8+ T lymphocytes are more effective than Gag(181-189)CM9-specific CD8+ T lymphocytes at suppressing simian immunodeficiency virus replication in a functional in vitro assay

John T Loffredo et al. J Virol. 2005 Dec.

Abstract

Epitope-specific CD8+ T lymphocytes may play an important role in controlling human immunodeficiency virus (HIV)/simian immunodeficiency virus replication. Unfortunately, standard cellular assays do not measure the antiviral efficacy (the ability to suppress virus replication) of CD8+ T lymphocytes. Certain epitope-specific CD8+ T lymphocytes may be better than others at suppressing viral replication. We compared the antiviral efficacy of two immunodominant CD8+ T lymphocyte responses--Tat(28-35)SL8 and Gag(181-189)CM9--by using a functional in vitro assay. Viral suppression by Tat-specific CD8+ T lymphocytes was consistently greater than that of Gag-specific CD8+ T lymphocytes. Such differences in antigen-specific CD8+-T-lymphocyte efficacy may be important for selecting CD8+ T lymphocyte epitopes for inclusion in future HIV vaccines.

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Figures

FIG. 1.
FIG. 1.
VSA schematic. (A) Target cells are freshly isolated PBMC, depleted of CD8+ cells, and activated with phytohemagglutinin (PHA). (B) Effector cells are SIV-specific in vitro-stimulated CD8+ T cells that are sorted to high specificity. (C) After a 4-h incubation of the target cells with SIVmac239, we combined target and effector cells at E:T ratios of 1:10, and 1:20. The cocultures were maintained for 8 to 11 days. 0.5 ml of supernatant was taken every 2 days for vRNA quantification. MOI, multiplicity of infection.
FIG. 2.
FIG. 2.
Day 8 intracellular Gag p27 staining of representative VSA results with Tat28-35SL8- and Gag181-189CM9-specific CD8+ T-lymphocytes from a single macaque (animal 2125). Results for MHC class I-matched effector and target cells (A) and MHC-mismatched effector (Mamu-A*01+) and target (Mamu-A*01−) cells (B) at an E:T of 1:10 are shown. Viral suppression only occurred in an MHC class I-restricted fashion.
FIG. 3.
FIG. 3.
Quantitative PCR of representative VSA results with Tat28-35SL8- and Gag181-189CM9-specific CD8+ T lymphocytes from macaque 2125. Results for MHC class I-matched effector and target cells (A) MHC-mismatched effector (Mamu-A*01+) and target (Mamu-A*01−) cells (B) at an E:T of 1:10 are shown. Viral suppression only occurred in an MHC class I-restricted fashion.
FIG. 4.
FIG. 4.
Day 8 viral suppression by Tat28-35SL8- and Gag181-189CM9-specific CD8+ T lymphocytes derived from several SIV-infected macaques (animal identification number shown below bars) at an E:T ratio of 1:10 as measured by fold reduction of intracellular Gag p27 (A) and fold reduction of vRNA copies/ml (B). Bars: ▪, Tat-specific cells; □, Gag-specific cells.
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