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

Publication date: 19 December 2017
Source:Cell Reports, Volume 21, Issue 12
Author(s): 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
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.

Graphical abstract

Teaser

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.


http://ift.tt/2ktstPT