Vieira, VA;
Adland, E;
Malone, DFG;
Martin, MP;
Groll, A;
Ansari, MA;
Garcia-Guerrero, MC;
... Goulder, PJR; + view all
(2021)
An HLA-I signature favouring KIR-educated Natural Killer cells mediates immune control of HIV in children and contrasts with the HLA-B-restricted CD8+T-cell-mediated immune control in adults.
PLOS Pathogens
, 17
(11)
, Article e1010090. 10.1371/journal.ppat.1010090.
Preview |
Text
Bamford_journal.ppat.1010090.pdf - Published Version Download (2MB) | Preview |
Abstract
Natural Killer (NK) cells contribute to HIV control in adults, but HLA-B-mediated T-cell activity has a more substantial impact on disease outcome. However, the HLA-B molecules influencing immune control in adults have less impact on paediatric infection. To investigate the contribution NK cells make to immune control, we studied >300 children living with HIV followed over two decades in South Africa. In children, HLA-B alleles associated with adult protection or disease-susceptibility did not have significant effects, whereas Bw4 (p = 0.003) and low HLA-A expression (p = 0.002) alleles were strongly associated with immunological and viral control. In a comparator adult cohort, Bw4 and HLA-A expression contributions to HIV disease outcome were dwarfed by those of protective and disease-susceptible HLA-B molecules. We next investigated the immunophenotype and effector functions of NK cells in a subset of these children using flow cytometry. Slow progression and better plasma viraemic control were also associated with high frequencies of less terminally differentiated NKG2A+NKp46+CD56dim NK cells strongly responsive to cytokine stimulation and linked with the immunogenetic signature identified. Future studies are indicated to determine whether this signature associated with immune control in early life directly facilitates functional cure in children.
| Type: | Article |
|---|---|
| Title: | An HLA-I signature favouring KIR-educated Natural Killer cells mediates immune control of HIV in children and contrasts with the HLA-B-restricted CD8+T-cell-mediated immune control in adults |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1371/journal.ppat.1010090 |
| Publisher version: | https://doi.org/10.1371/journal.ppat.1010090 |
| Language: | English |
| Additional information: | This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication. See: https://creativecommons.org/publicdomain/zero/1.0/ |
| Keywords: | Science & Technology, Life Sciences & Biomedicine, Microbiology, Parasitology, Virology, T-LYMPHOCYTE RESPONSES, NK CELLS, C EXPRESSION, 1ST YEAR, INFECTION, IMPACT, GAG, ESCAPE, CYTOTOXICITY, FREQUENCY |
| 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 UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10140436 |
Archive Staff Only
 |
View Item |
