UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Plasma IL-5 but Not CXCL13 Correlates With Neutralization Breadth in HIV-Infected Children

Roider, J; Zachary Porterfield, J; Ogongo, P; Muenchhoff, M; Adland, E; Groll, A; Morris, L; ... Leslie, A; + view all (2019) Plasma IL-5 but Not CXCL13 Correlates With Neutralization Breadth in HIV-Infected Children. Frontiers in Immunology , 10 , Article 1497. 10.3389/fimmu.2019.01497. Green open access

[thumbnail of Kloverpris_Plasma IL-5 but not CXCL13 correlates with neutralization breadth in HIV-infected children_VoR.pdf]
Preview
Text
Kloverpris_Plasma IL-5 but not CXCL13 correlates with neutralization breadth in HIV-infected children_VoR.pdf - Published Version

Download (863kB) | Preview

Abstract

Children may be the optimal target for HIV vaccine development as they generate substantially more frequent and more potent broadly HIV neutralizing antibodies (bnAbs) than adults. Development of a biomarker that correlates with neutralization breadth in this group could function as a powerful tool to facilitate the development of an HIV vaccine. Previously, we observed that this preferential ability in HIV-infected children over adults to generate bnAbs is associated with an enrichment of circulating follicular helper T-cells (TFH) with an effector phenotype, and the presence of IL-21 secreting HIV-specific TFH within lymphoid tissue germinal centers (GC). In adults, bnAbs development has been linked with high plasma levels of CXCL13, a chemoattractant for CXCR5-expressing TFH cells to the lymph node GC. We sought to test this relationship in HIV-infected children, but found no association between neutralization breadth and plasma levels of CXCL13, or with the Th2 cytokines IL-4 and IL-13, or the TFH associated factor Activin A. However, we did find an unexpected association between plasma IL-5 levels and bnAb development in these children. Importantly, although CXCL13 correlated with total circulating TFH cells, it was not associated with effector TFH. Additionally, raised CXCL13 expression was associated with a lower CD4 percentage, higher viral load and a loss of immune function, implying it is associated with progressive disease rather than HIV-specific GC activity in these subjects. Taken together, our data suggests that IL-5 should be evaluated further as a candidate plasma biomarker for HIV neutralization breadth and for monitoring vaccine responses in the pediatric age group.

Type: Article
Title: Plasma IL-5 but Not CXCL13 Correlates With Neutralization Breadth in HIV-Infected Children
Open access status: An open access version is available from UCL Discovery
DOI: 10.3389/fimmu.2019.01497
Publisher version: https://doi.org/10.3389/fimmu.2019.01497
Language: English
Additional information: Copyright © 2019 Roider, Porterfield, Ogongo, Muenchhoff, Adland, Groll, Morris, Moore, Ndung'u, Kløverpris, Goulder and Leslie. 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.
Keywords: CXCL13, IL-5, Activin A, broadly neutralizing antibodies (bnAbs), pediatric HIV, plasma markers, HIV neutralization breadth, T-follicular helper cells (Tfh)
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/10080275
Downloads since deposit
61Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item