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Differing natural killer cell, T cell and antibody profiles in antiretroviral-naive HIV-1 viraemic controllers with and without protective HLA alleles.
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- Author(s): Moyano, Ana; Ndlovu, Bongiwe; Mbele, Msizi; Naidoo, Kewreshini; Khan, Nasreen; Mann, Jaclyn K.; Ndung'u, Thumbi
- Source:
PLoS ONE; 6/2/2023, Vol. 17 Issue 6, p1-20, 20p- Subject Terms:
- Source:
- Additional Information
- 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-. [ABSTRACT FROM AUTHOR]
- Abstract: Copyright of PLoS ONE is the property of Public Library of Science and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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