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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Antigen production after latency reversal and expression of inhibitory receptors in CD8+ T cells limit the killing of HIV-1 reactivated cells
Frontiers in Immunology, Volume 10, No. JAN, Article 3162, Year 2019
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Description
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. © 2019 Ruiz, Blanch-Lombarte, Jimenez-Moyano, Ouchi, Mothe, Peña, Galvez, Genescà, Martinez-Picado, Goulder, Barnard, Howell, Clotet and Prado.
Authors & Co-Authors
Ruiz, Alba
Spain, Badalona
Irsicaixa Aids Research Institute
Spain, Cerdanyola Del Valles
Universitat Autònoma de Barcelona
Jiménez-Moyano, Esther
Spain, Badalona
Irsicaixa Aids Research Institute
Ouchi, Dan
Spain, Badalona
Irsicaixa Aids Research Institute
Mothe, Beatriz
Spain, Badalona
Irsicaixa Aids Research Institute
Spain, Vic
Universitat de Vic - Universitat Central de Catalunya Uvic-ucc
Peña, Ruth
Spain, Badalona
Irsicaixa Aids Research Institute
Gálvez, Cristina
Spain, Badalona
Irsicaixa Aids Research Institute
Spain, Cerdanyola Del Valles
Universitat Autònoma de Barcelona
Martínez-Picado, Javier
Spain, Badalona
Irsicaixa Aids Research Institute
Spain, Vic
Universitat de Vic - Universitat Central de Catalunya Uvic-ucc
Spain, Barcelona
Institució Catalana de Recerca I Estudis Avançats
Goulder, Philip Jeremy Renshaw
United Kingdom, Oxford
University of Oxford Medical Sciences Division
Clotet, Bonaventura
Spain, Badalona
Irsicaixa Aids Research Institute
Spain, Vic
Universitat de Vic - Universitat Central de Catalunya Uvic-ucc
Prado, Julia Garcia
Spain, Badalona
Irsicaixa Aids Research Institute
Spain, Cerdanyola Del Valles
Universitat Autònoma de Barcelona
Statistics
Citations: 13
Authors: 10
Affiliations: 6
Identifiers
Doi:
10.3389/fimmu.2018.03162
ISSN:
16643224
Research Areas
Infectious Diseases