CD8+ T cell-restricted immunity is important in the control of HIV-1 infection, but continued immune activation results in CD8+ T cell dysfunction. Early initiation of antiretroviral treatment (ART) and the duration of ART have been associated with immune reconstitution. Here, we evaluated whether restoration of CD8+ T cell function in HIV-1-infected individuals was dependent on early initiation of ART. HIV-specific CD107a, IFNγ, IL-2, TNFα and MIP-1β expression by CD8+ T cells and the frequency of CD8+ T cells expressing PD-1, 2B4 and CD160 were measured by flow cytometry. The frequency of CD8+ T cells expressing the inhibitory markers PD-1, 2B4 and CD160 was lower in ART-treated individuals compared with ART-naïve individuals and similar to the frequency in HIV-uninfected controls. The expression of the three markers was similarly independent of when therapy was initiated. Individuals treated before seroconversion displayed an HIV-specific CD8+ T cell response that included all five functional markers; this was not observed in individuals treated after seroconversion or in ART-naïve individuals. In summary, ART appears to restore the total CD8+ T cell population to a less exhausted phenotype, independent of the time point of initiation. However, to preserve multifunctional, HIV-1-specific CD8+ T cells, ART might have to be initiated before seroconversion.
This article explores a question format consisting of `you say' plus a version of what the co-participant has said, which is used to ask for confirmation of something said in an earlier sequence. Questions using this you say x format often request not only confirmation but also accounts and can, on occasions, be taken as challenging the interactional balance, that is, be treated as disaffiliative. The article investigates the sequential, prosodic and grammatical conditions for affiliative and disaffiliative uses of you say x questions and discusses the potential institution specificity of the phenomenon. It is found that the clearly disaffiliative you say x questions are parts of dispreferred and disaligning moves, that they have `marked' prosody, that they raise problems, and that they are most often prefaced by `objecting' particles. Affiliative you say x questions are aligning next sequences in environments where the focus is on information delivery. They have `unmarked' prosody and they contribute to getting information on record. You say x questions which call for accounts without being clearly disaffiliative, are also examined. Even though they often raise problematic issues, they are not sequentially disaligning and have less `marked' prosody than the disaffiliative cases.
HAART improves the ability of NK cells to mediate ADCC after 6 months. This improvement does not correlate with general immune restoration, as measured by CD4 T-cell counts, but rather to a decrease in the frequency of NK cells expressing CCR7 and CD27.
Standard in vitro assays measuring one or several cytokines do not correlate with the functional viral suppressive capacity of CD8(+) T cells from HIV-1-positive individuals. The best correlation of viral suppression was found to be CD57 expression. CD57 expression correlated with the duration of ART, suggesting that ART restores the cytotoxic capacity of CD8(+) T lymphocytes.
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