HIV-Specific CD8+ T Cells Exhibit Reduced and Differentially Regulated Cytolytic Activity in Lymphoid Tissue

Autor: Morgan A. Reuter, Perla M. Del Rio Estrada, Marcus Buggert, Constantinos Petrovas, Sara Ferrando-Martinez, Son Nguyen, Alberto Sada Japp, Yuria Ablanedo-Terrazas, Amaranta Rivero-Arrieta, Leticia Kuri-Cervantes, Heidi M. Gunzelman, Emma Gostick, David A. Price, Richard A. Koup, Ali Naji, David H. Canaday, Gustavo Reyes-Terán, Michael R. Betts
Jazyk: angličtina
Rok vydání: 2017
Předmět:
Zdroj: Cell Reports, Vol 21, Iss 12, Pp 3458-3470 (2017)
Druh dokumentu: article
ISSN: 2211-1247
DOI: 10.1016/j.celrep.2017.11.075
Popis: Summary: 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. : Reuter et al. show that lymphoid tissue CD8+ T cells from HIV-infected and uninfected individuals do not possess phenotypic, functional, or transcriptional regulatory properties of cytolytic T cells equivalent to those found in circulation. Their findings suggest that the failure to eliminate HIV could be related to compartmentalized CD8+ T cell function favoring noncytolytic responses in lymphoid tissue. Keywords: HIV, lymphoid tissue, CD8+ T cells, cytotoxicity
Databáze: Directory of Open Access Journals