Muenchhoff, M;
Adland, E;
Roider, J;
Kløverpris, H;
Leslie, A;
Boehm, S;
Keppler, OT;
... Goulder, PJR; + view all
(2019)
Differential Pathogen-Specific Immune Reconstitution in Antiretroviral Therapy-Treated Human Immunodeficiency Virus-Infected Children.
The Journal of infectious diseases
, 219
(9)
pp. 1407-1417.
10.1093/infdis/jiy668.
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Abstract
Background. Susceptibility to coinfections in human immunodefciency virus (HIV)-infected patients remains increased despite antiretroviral therapy (ART). To elucidate mechanisms involved in immune reconstitution, we studied immune activation, immune exhaustion, and HIV- and copathogen-specifc T-cell responses in children before and afer ART. Methods. We prospectively enrolled 25 HIV-infected children to study HIV-, cytomegalovirus (CMV)-, and tuberculosis (TB)- specifc T-cell responses before and 1 year afer initiation of ART using intracellular cytokine (interleukin-2, interferon-γ, tumor necrosis factor-α) staining assays afer in vitro stimulation. We further measured expression of activation, immune exhaustion, and memory phenotype markers and studied proliferative responses afer antigen stimulation. Results. We observed diferential, pathogen-specifc changes afer 1 year of ART in cytokine profles of CD4 T-cell responses that were associated with shifs in memory phenotype and decreased programmed cell death 1 (PD-1) expression. Te proliferative capacity of HIV- and PPD-specifc responses increased afer 1 year of ART. Of note, the recovery of CMV- and TB-specifc responses was correlated with a decrease in PD-1 expression (r = 0.83, P = .008 and r = 0.81, P = .0007, respectively). Conclusions. Reconstitution of immune responses on ART is associated with alterations in T-cell phenotype, function, and PD-1 expression that are distinct for HIV, TB, and CMV. Te PD-1 pathway represents a potential target for immunotherapy in HIVinfected patients on ART with insufcient immune reconstitution.
| Type: | Article |
|---|---|
| Title: | Differential Pathogen-Specific Immune Reconstitution in Antiretroviral Therapy-Treated Human Immunodeficiency Virus-Infected Children |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1093/infdis/jiy668 |
| Publisher version: | https://doi.org/10.1093/infdis/jiy668 |
| Language: | English |
| Additional information: | Published by Oxford University Press for the Infectious Diseases Society of America. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
| Keywords: | HIV, antiretroviral therapy, cytomegalovirus, tuberculosis |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10080361 |
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