Elite controller CD8+ T cells exhibit comparable viral inhibition capacity, but better sustained effector properties compared to chronic progressors

精英控制者 CD8+ T 细胞表现出相当的病毒抑制能力,但与慢性进展者相比,其持续效应特性更好

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作者:David Shasha, Dan Karel, Olivia Angiuli, Adam Greenblatt, Musie Ghebremichael, Xu Yu, Filippos Porichis, Bruce D Walker

Abstract

Mechanisms modulating HIV-specific CD8+ T cell-mediated viral inhibition are not well defined. To delineate features of effective control, we compared the ability of CD8+ T cells from HIV ECs and CPs to inhibit HIV ex vivo. ECs showed superior inhibition compared to HAART-treated or untreated CPs in a typical VIA in which CD8+ T cells are rested 3 d before use (P = 0.025). In contrast, comparable antiviral activity was observed in freshly thawed cells. Rested CD8+ T cells underwent apoptosis with preferential loss of HIV-specific cells. EC CD8+ T cells showed greater capacity to sustain polyfunctionality ex vivo compared with those of CPs, and incubation of CD8+ T cells with IL-15 augmented inhibition. These results indicate that superior ex vivo inhibition of viral replication by CD8+ T cells from ECs is associated with enhanced retention of functional qualities and that in vitro antiviral function is enhanced by IL-15.

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