title: Substantial intrapatient differences in the breadth and specificity of HIV-specific CD8+ T-cell interferon-gamma and proliferation responses.
abstract: HIV vaccine design and evaluation require a better understanding of protective immune responses. HIV-specific CD8+ T-cell responses have been characterized extensively using interferon-gamma (IFN-gamma) enzyme-linked immunosorbent spot (ELISPOT) assays, which do not always correlate with control of viral replication or disease progression. Alternative aspects of CD8+ T-cell responses, in particular those associated with a central memory (Tcm) phenotype, may be more protective against disease progression. To determine the extent that the breadth and specificity of HIV-specific CD8+ T-cell responses differ based on immunological readout, we screened in HIV-infected Kenyan sex workers for responses to HIV Env using IFN-gamma ELISPOT and 6-day carboxyfluorescein succinimidyl ester-based proliferation assays. This comparison revealed substantial differences in the epitopes recognized when the assay readout was IFN-gamma versus proliferation. Although 24 and 41 IFN-gamma and proliferative responses were identified, overlapping specificity was observed for only 5 responses. Breadth also differed between assays in several patients. Env-specific IFN-gamma breadth was found to correlate inversely with CD4 count (r = -0.66, P = 0.005), although this was not the case for proliferation. These data suggest that efforts to define HIV-specific CD8+ T-cell responses may need to be revisited using additional immunological readouts.
authors.affiliation: Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Lyle R
authors.initials: LR
authors.lastname: McKinnon
authors.forename: T Blake
authors.initials: TB
authors.lastname: Ball
authors.forename: Charles
authors.initials: C
authors.lastname: Wachihi
authors.forename: Nyakio
authors.initials: N
authors.lastname: Chinga
authors.forename: Anne
authors.initials: A
authors.lastname: Maingi
authors.forename: Ma
authors.initials: M
authors.lastname: Luo
authors.forename: Keith R
authors.initials: KR
authors.lastname: Fowke
authors.forename: Francis A
authors.initials: FA
authors.lastname: Plummer