Lund University Publications

@article{c9c387fb-7979-4f73-ab73-e5d757669d67,
  abstract     = {{<p>HIV-2 is less pathogenic compared to HIV-1. Still, disease progression may develop in aviremic HIV-2 infection, but the driving forces and mechanisms behind such development are unclear. Here, we aimed to reveal the immunophenotypic pattern associated with CD8 T-cell pathology in HIV-2 infection, in relation to viremia and markers of disease progression. The relationships between pathological differences of the CD8 T-cell memory population and viremia were analyzed in blood samples obtained from an occupational cohort in Guinea-Bissau, including HIV-2 viremic and aviremic individuals. For comparison, samples from HIV-1- or dually HIV-1/2-infected and seronegative individuals were obtained from the same cohort. CD8 T-cell exhaustion was evaluated by the combined expression patterns of activation, stimulatory and inhibitory immune checkpoint markers analyzed using multicolor flow cytometry and advanced bioinformatics. Unsupervised multidimensional clustering analysis identified a cluster of late differentiated CD8 T-cells expressing activation (CD38+, HLA-DR<sup>int/high</sup>), co-stimulatory (CD226+/-), and immune inhibitory (2B4+, PD-1<sup>high</sup>, TIGIT<sup>high</sup>) markers that distinguished aviremic from viremic HIV-2, and treated from untreated HIV-1-infected individuals. This CD8 T-cell population displayed close correlations to CD4%, viremia, and plasma levels of IP-10, sCD14 and beta-2 microglobulin in HIV-2 infection. Detailed analysis revealed that aviremic HIV-2-infected individuals had higher frequencies of exhausted TIGIT+ CD8 T-cell populations lacking CD226, while reduced percentage of stimulation-receptive TIGIT-CD226+ CD8 T-cells, compared to seronegative individuals. Our results suggest that HIV-2 infection, independent of viremia, skews CD8 T-cells towards exhaustion and reduced co-stimulation readiness. Further knowledge on CD8 T-cell phenotypes might provide help in therapy monitoring and identification of immunotherapy targets.</p>}},
  author       = {{Scharf, Lydia and Pedersen, Christina B. and Johansson, Emil and Lindman, Jacob and Olsen, Lars R and Buggert, Marcus and Wilhelmson, Sten and Månsson, Fredrik and Esbjörnsson, Joakim and Biague, Antonio and Medstrand, Patrik and Norrgren, Hans and Karlsson, Annika C. and Jansson, Marianne}},
  issn         = {{1664-3224}},
  keywords     = {{aviremic; CD226; CD8 T cell phenotypes; costimulation; HIV-2; immune activation; T cell exhaustion; TIGIT}},
  language     = {{eng}},
  month        = {{10}},
  publisher    = {{Frontiers Media S. A.}},
  series       = {{Frontiers in Immunology}},
  title        = {{Inverted CD8 T-Cell Exhaustion and Co-Stimulation Marker Balance Differentiate Aviremic HIV-2-Infected From Seronegative Individuals}},
  url          = {{http://dx.doi.org/10.3389/fimmu.2021.744530}},
  doi          = {{10.3389/fimmu.2021.744530}},
  volume       = {{12}},
  year         = {{2021}},
}