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Therapeutic immunisation benefits mucosal-associated invariant T-cell recovery in contrast to IL-2, GM-CSF, and rhGH addition in HIV-1+ treated patients: individual case reports from phase I trial

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Title: Therapeutic immunisation benefits mucosal-associated invariant T-cell recovery in contrast to IL-2, GM-CSF, and rhGH addition in HIV-1+ treated patients: individual case reports from phase I trial
Authors: Cocker, ATH
Greathead, L
Herasimtschuk, AA
Mandalia, S
Kelleher, P
Imami, N
Item Type: Journal Article
Abstract: Mucosal-associated invariant T (MAIT) cell populations are reduced in frequency in HIV-1+ patients, and this disruption is associated with systemic immune activation. Reconstitution of MAIT frequency may benefit HIV-1-infected individuals; however, only recently has in vivo work been endeavored. Treatment with interleukin (IL)-2, granulocyte-macrophage colony-stimulating factor (GM-CSF), and recombinant human growth hormone (rhGH) immunotherapy combined with an HIV-1 vaccine in the context of antiretroviral therapy (ART) has shown to reconstitute CD4 T cell population numbers and function. In this study cryopreserved peripheral blood mononuclear cells (PBMCs) from 12 HIV-1+ patients who were undergoing a combination of HIV-1 vaccine and/or IL-2, GM-CSF and rhGH immunotherapy in conjunction with ART were analyzed to assess the potential of this treatment to promote MAIT cell proliferation. PBMCs were thawed from study baseline, weeks 2 and 48 time points, fluorescently stained for MAIT cell markers, and assessed by flow cytometric analysis. Matched pairs and intergroup results were statistically compared using appropriate methods. MAIT cell frequency was increased from baseline at 48 weeks in participants who received vaccine only, whereas individuals receiving IL-2, GM-CSF, and rhGH immunotherapy with or without vaccine did not show additional benefit. Although IL-2, GM-CSF, and rhGH treatment promotes CD4 T cell reconstitution and HIV-1-specific T cell function, it does not support MAIT cell recovery in patients on suppressive ART. Therapeutic immunization however has a positive effect, highlighting the importance of aiming for balanced promotion of T cell population reconstitution to impact on HIV-1 transmission and pathogenesis.
Issue Date: 5-Mar-2019
Date of Acceptance: 30-Dec-2018
URI: http://hdl.handle.net/10044/1/66925
DOI: https://doi.org/10.1089/aid.2018.0176
ISSN: 0889-2229
Publisher: Mary Ann Liebert Inc
Journal / Book Title: AIDS Research and Human Retroviruses
Volume: 35
Issue: 3
Copyright Statement: © 2019, Mary Ann Liebert, Inc., publishers.
Sponsor/Funder: Westminster Medical School Research Trust
Medical Research Council (MRC)
Medical Research Council
Westminster Medical School Research Trust
Westminster Medical School Research Trust
St Stephen's Aids Trust
St Stephen's Aids Trust
Westminster Medical School Research Trust
Medical Research Council
Funder's Grant Number: PMS/MMS - 13/14 - 4161 (IMM 2)
G0501957
G0501957
JRC 10 / 11 R F 002
PMS/MMS-12/13-4011 (Imm.1)
N/A
n/a
JRC FS 002 03/15-16
G0501957
Keywords: Science & Technology
Life Sciences & Biomedicine
Immunology
Infectious Diseases
Virology
HIV-1
MAIT cells
ART
immunotherapy
therapeutic immunization
immunological reconstitution
ART
HIV-1
MAIT cells
immunological reconstitution
immunotherapy
therapeutic immunization
1103 Clinical Sciences
Virology
Publication Status: Published
Article Number: AID.2018.0176
Online Publication Date: 2019-01-02
Appears in Collections:Department of Infectious Diseases