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

• Published in: Cell reports (Cambridge) Vol. 21; no. 12; pp. 3458 - 3470
• Main Authors: 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, Price, David A., Koup, Richard A., Naji, Ali, Canaday, David H., Reyes-Terán, Gustavo, Betts, Michael R.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 19.12.2017; Elsevier
• Subjects: CD8+ T cells; cytotoxicity; HIV; lymphoid tissue; Medicin och hälsovetenskap; CD8+ T cells; HIV; lymphoid tissue; cytotoxicity; CD8(+) T cells
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2017.11.075

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. [Display omitted] •CD8+ T cells in quiescent lymphoid tissues do not express markers of cytotoxicity•Lymphoid tissue HIV-specific CD8+ T cells do not possess full cytolytic markers•Noncytolytic CXCR5+ CD8+ T cells in lymphoid tissue associate with viral control 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.