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HIV-specific CD8 + T cells exhibit reduced and differentially regulated Cytolytic activity in Lymphoid tissue

Reuter, Morgan A., Del Rio Estrada, Perla M., Buggert, Marcus, Petrovas, Constantinos, Ferrando-Martinez, Sara, Nguyen, Son, Sada Japp, Alberto, Ablanedo-Terrazas, Yuria, Rivero-Arrieta, Amaranta, Kuri-Cervantes, Leticia, Gunzelman, Heidi M., Gostick, Emma Gostick, Price, David, Koup, Richard A., Naji, Ali, Canaday, David H., Reyes-Terán, Gustavo and Betts, Michael R. 2017. HIV-specific CD8 + T cells exhibit reduced and differentially regulated Cytolytic activity in Lymphoid tissue. Cell Reports 21 (12) , pp. 3458-3470. 10.1016/j.celrep.2017.11.075

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Elimination of lymphoid tissue reservoirs is a key component of HIV eradication strategies. CD8+ T cells play a critical role in control of HIV, but their functional attributes in lymph nodes (LNs) remain unclear. Here, we show that memory, follicular CXCR5+, and HIV-specific CD8+ T cells from LNs do not manifest the properties of cytolytic CD8+ T cells. While the frequency of follicular CXCR5+ CD8+ T cells was strongly inversely associated with peripheral viremia, this association was not dependent on cytolytic CXCR5+ CD8+ T cells. Moreover, the poor cytolytic activity of LN CD8+ T cells was linked to a compartmentalized dissociation between effector programming and the transcription factor T-bet. In line with this, activation of LN CD8+ T cells only partially induced the acquisition of cytolytic functions relative to peripheral blood CD8+ T cells. These results suggest that a state of immune privilege against CD8+ T cell-mediated cytolysis exists in lymphoid tissue, potentially facilitating the persistence of HIV.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Publisher: Cell Press
ISSN: 2211-1247
Date of First Compliant Deposit: 5 January 2018
Date of Acceptance: 21 November 2017
Last Modified: 08 Jan 2018 15:59

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