HIV-specific CD8 T Cells from Elite Controllers Rapidly Up-regulate Perforin after Stimulation
Adam Hersperger*1, P Sheth2, L Shin2, R Kaul2, and M Betts1
1Univ of Pennsylvania, Philadelphia, US and 2Univ of Toronto, Canada
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.