[Show abstract][Hide abstract] ABSTRACT: CD8+ T lymphocytes appear to play a role in controlling human immunodeficiency virus (HIV) replication, yet routine immunological
assays do not measure the antiviral efficacy of these cells. Furthermore, it has been suggested that CD8+ T cells that recognize epitopes derived from proteins expressed early in the viral replication cycle can be highly efficient.
We used a functional in vitro assay to assess the abilities of different epitope-specific CD8+ T-cell lines to control simian immunodeficiency virus (SIV) replication. We compared the antiviral efficacies of 26 epitope-specific
CD8+ T-cell lines directed against seven SIV epitopes in Tat, Nef, Gag, Env, and Vif that were restricted by either Mamu-A*01
or Mamu-A*02. Suppression of SIV replication varied depending on the epitope specificities of the CD8+ T cells and was unrelated to whether the targeted epitope was derived from an early or late viral protein. Tat28-35SL8- and Gag181-189CM9-specific CD8+ T-cell lines were consistently superior at suppressing viral replication compared to the other five SIV-specific CD8+ T-cell lines. We also investigated the impact of viral escape on antiviral efficacy by determining if Tat28-35SL8- and Gag181-189CM9-specific CD8+ T-cell lines could suppress the replication of an escaped virus. Viral escape abrogated the abilities of Tat28-35SL8- and Gag181-189CM9-specific CD8+ T cells to control viral replication. However, gamma interferon (IFN-γ) enzyme-linked immunospot and IFN-γ/tumor necrosis
factor alpha intracellular-cytokine-staining assays detected cross-reactive immune responses against the Gag escape variant.
Understanding antiviral efficacy and epitope variability, therefore, will be important in selecting candidate epitopes for
an HIV vaccine.
Full-text · Article · Apr 2007 · Journal of Virology
[Show abstract][Hide abstract] 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—Tat28-35SL8 and Gag181-189CM9—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.
Full-text · Article · Jan 2006 · Journal of Virology