Moyano, Ana;
Ndlovu, Bongiwe;
Mbele, Msizi;
Naidoo, Kewreshini;
Khan, Nasreen;
Mann, Jaclyn K;
Ndung'u, Thumbi;
(2023)
Differing natural killer cell, T cell and antibody profiles in antiretroviral-naive HIV-1 viraemic controllers with and without protective HLA alleles.
PLoS One
, 18
(6)
, Article e0286507. 10.1371/journal.pone.0286507.
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Abstract
Previous work suggests that HIV controllers with protective human leukocyte antigen class I alleles (VC+) possess a high breadth of Gag-specific CD8+ T cell responses, while controllers without protective alleles (VC-) have a different unknown mechanism of control. We aimed to gain further insight into potential mechanisms of control in VC+ and VC-. We studied 15 VC+, 12 VC- and 4 healthy uninfected individuals (UI). CD8+ T cell responses were measured by ELISpot. Flow cytometry was performed to analyse surface markers for activation, maturation, and exhaustion on natural killer (NK) cell and T cells, as well as cytokine secretion from stimulated NK cells. We measured plasma neutralization activity against a panel of 18 Env-pseudotyped viruses using the TZM-bl neutralization assay. We found no significant differences in the magnitude and breadth of CD8+ T cell responses between VC+ and VC-. However, NK cells from VC- had higher levels of activation markers (HLA-DR and CD38) (p = 0.03), and lower cytokine expression (MIP-1β and TNF-α) (p = 0.05 and p = 0.04, respectively) than NK cells from VC+. T cells from VC- had higher levels of activation (CD38 and HLA-DR co-expression) (p = 0.05), as well as a trend towards higher expression of the terminal differentiation marker CD57 (p = 0.09) when compared to VC+. There was no difference in overall neutralization breadth between VC+ and VC- groups, although there was a trend for higher neutralization potency in the VC- group (p = 0.09). Altogether, these results suggest that VC- have a more activated NK cell profile with lower cytokine expression, and a more terminally differentiated and activated T cell profile than VC+. VC- also showed a trend of more potent neutralizing antibody responses that may enhance viral clearance. Further studies are required to understand how these NK, T cell and antibody profiles may contribute to differing mechanisms of control in VC+ and VC-.
| Type: | Article |
|---|---|
| Title: | Differing natural killer cell, T cell and antibody profiles in antiretroviral-naive HIV-1 viraemic controllers with and without protective HLA alleles |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1371/journal.pone.0286507 |
| Publisher version: | https://doi.org/10.1371/journal.pone.0286507 |
| Language: | English |
| Additional information: | © 2023 Moyano et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/). |
| Keywords: | Humans, HIV-1, HIV Infections, HIV Non-Progressors, Alleles, CD8-Positive T-Lymphocytes, Killer Cells, Natural, HLA-DR Antigens, Cytokines |
| 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-pp.ucl.ac.uk/id/eprint/10171864 |
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