Background:  Evidence suggests that CD8 T cells are important to the control of HIV replication, but the mechanism by which this occurs is unclear. In fact, few differences in CD8 T cell cytotoxic function have been observed to date in HIV-infected subjects that control viral replication compared to individuals that have an unfavorable disease course.

Methods:  We have recently discovered the novel ability of human CD8 T cells to rapidly up-regulate perforin following antigen-specific stimulation. Using polychromatic flow cytometry, we measured perforin up-regulation, cytokine production, and degranulation following stimulation of ex vivo CD8 T cells from HIV-infected elite controllers, viremic controllers, and chronically infected individuals.

Results:  We observe that on average 40% of the total CD8 T cell response in elite controllers up-regulates perforin following HIV-specific stimulation versus about 15% of the response in the other cohorts. However, there is no difference in the proportion of the response that produces interferon-g (IFN-g) between groups. Additionally, the cells that up-regulate perforin are of largely an effector/effector memory phenotype.

Conclusions:  The rapid perforin up-regulation displayed by CD8 T cells in elite controllers may contribute to the superior control of HIV replication in these subjects.