Differing natural killer cell, T cell and antibody profiles in antiretroviral-naive HIV-1 viraemic controllers with and without protective HLA alleles.
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 i...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2023-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0286507 |
| _version_ | 1827931711147606016 |
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| author | Ana Moyano Bongiwe Ndlovu Msizi Mbele Kewreshini Naidoo Nasreen Khan Jaclyn K Mann Thumbi Ndung'u |
| author_facet | Ana Moyano Bongiwe Ndlovu Msizi Mbele Kewreshini Naidoo Nasreen Khan Jaclyn K Mann Thumbi Ndung'u |
| author_sort | Ana Moyano |
| collection | DOAJ |
| description | 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-. |
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| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-03-13T06:56:32Z |
| publishDate | 2023-01-01 |
| publisher | Public Library of Science (PLoS) |
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| spelling | doaj.art-1036a0e035574194998ef71454b4da012023-06-07T05:31:58ZengPublic Library of Science (PLoS)PLoS ONE1932-62032023-01-01186e028650710.1371/journal.pone.0286507Differing natural killer cell, T cell and antibody profiles in antiretroviral-naive HIV-1 viraemic controllers with and without protective HLA alleles.Ana MoyanoBongiwe NdlovuMsizi MbeleKewreshini NaidooNasreen KhanJaclyn K MannThumbi Ndung'uPrevious 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-.https://doi.org/10.1371/journal.pone.0286507 |
| spellingShingle | Ana Moyano Bongiwe Ndlovu Msizi Mbele Kewreshini Naidoo Nasreen Khan Jaclyn K Mann Thumbi Ndung'u Differing natural killer cell, T cell and antibody profiles in antiretroviral-naive HIV-1 viraemic controllers with and without protective HLA alleles. PLoS ONE |
| title | Differing natural killer cell, T cell and antibody profiles in antiretroviral-naive HIV-1 viraemic controllers with and without protective HLA alleles. |
| title_full | Differing natural killer cell, T cell and antibody profiles in antiretroviral-naive HIV-1 viraemic controllers with and without protective HLA alleles. |
| title_fullStr | Differing natural killer cell, T cell and antibody profiles in antiretroviral-naive HIV-1 viraemic controllers with and without protective HLA alleles. |
| title_full_unstemmed | Differing natural killer cell, T cell and antibody profiles in antiretroviral-naive HIV-1 viraemic controllers with and without protective HLA alleles. |
| title_short | Differing natural killer cell, T cell and antibody profiles in antiretroviral-naive HIV-1 viraemic controllers with and without protective HLA alleles. |
| title_sort | differing natural killer cell t cell and antibody profiles in antiretroviral naive hiv 1 viraemic controllers with and without protective hla alleles |
| url | https://doi.org/10.1371/journal.pone.0286507 |
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