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Front. Immunol. | doi: 10.3389/fimmu.2018.03162

Antigen Production after Latency Reversal and Expression of Inhibitory Receptors in CD8+ T cells Limit the Killing of HIV-1 Reactivated cells

  • 1IrsiCaixa, Spain
  • 2Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol (IGTP), Spain
  • 3Autonomous University of Barcelona, Spain
  • 4Hospital Germans Trias i Pujol, Spain
  • 5Universitat de Vic - Universitat Central de Catalunya, Spain
  • 6Vall d'Hebron Research Institute (VHIR), Spain
  • 7Department of Paediatrics, Medical Sciences Division, University of Oxford, United Kingdom
  • 8Merck (United States), United States

The so-called shock and kill therapies aim to combine HIV-1 reactivation by latency-reversing agents (LRA) with immune clearance to purge the HIV-1 reservoir. The clinical use of LRA has demonstrated detectable perturbations in the HIV-1 reservoir without measurable reductions to date. Consequently, fundamental questions concerning the limitations of the recognition and killing of LRA-reactivated cells by effector cells such as CD8+ T cells remain to be answered. Here, we developed a novel experimental framework where we combine the use of cytotoxic CD8+ T-cell lines and ex vivo CD8+ T cells from HIV-1-infected individuals with functional assays of LRA-inducible reactivation to delineate immune barriers to clear the reservoir. Our results demonstrate the potential for early recognition and killing of reactivated cells by CD8+ T cells. However, the potency of LRAs when crossing the barrier for antigen presentation in target cells, together with the lack of expression of inhibitory receptors in CD8+ T cells, are critical events to maximize the speed of recognition and the magnitude of the killing of LRA-inducible provirus. Taken together, our findings highlight direct limitations in LRA potency and CD8+ T cell functional status to succeed in the cure of HIV-1 infection.

Keywords: HIV-1 reservoir, HIV-1 Immunogen, CTL (Cytotoxic T lymphocyte), shock and kill, HIV - human immunodeficiency virus, Inhibitory Receptor

Received: 14 Sep 2018; Accepted: 21 Dec 2018.

Edited by:

Francesca Chiodi, Karolinska Institute (KI), Sweden

Reviewed by:

Sarah Rowland-Jones, Nuffield Department of Medicine, Medical Sciences Division, University of Oxford, United Kingdom
Elisa Vicenzi, San Raffaele Hospital (IRCCS), Italy  

Copyright: © 2018 Ruiz, Blanch-Lombarte, Jimenez-Moyano, Mothe, Peña, Genescà, Goulder, Barnard, Howell, Clotet and G Prado. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Julia G Prado, IrsiCaixa, Barcelona, Spain, jgarciaprado@irsicaixa.es