Identification of NK subsets that exhibit enhanced ADCC against HIV-infected cells — ASN Events
  1. Schedule
  2. Poster Session One
  3. Identification of NK subsets that exhibit enhanced ADCC against HIV-infected cells

Identification of NK subsets that exhibit enhanced ADCC against HIV-infected cells (#139)

Anna C Hearps 1 2 3 , Hans Kek 1 4 , Laura Rikard-Bell 1 , Jingling Zhou 5 , Anthony Jaworowski 1 5
  1. Life Sciences Discipline, Burnet Institute, Melbourne, Victoria, Australia
  2. Department of Infectious Diseases, Monash University, Melbourne, VIC, Australia
  3. Department of Infectious Diseases, University of Melbourne, Melbourne, Victoria, Australia
  4. Department of Immunology, Monash University, Melbourne, VIC, Australia
  5. School of Applied Sciences, RMIT University, Melbourne, VIC, Australia

Background: Latent reservoirs of HIV persist in T cells and macrophages in people with HIV (PWH) despite antiretroviral therapy. HIV cure necessitates the targeted elimination of these reservoirs, with one strategy involving elimination of reactivated cells using immunotherapy with anti-HIV antibodies to enhance antibody-dependent cellular cytotoxicity (ADCC). We have previously identified antibodies that opsonise HIV-infected T cells and macrophages, but the NK cell subsets able to target these cells is unclear.

Methods: ADCC activity (identified by the degranulation marker CD107a) was assessed on NK cells in PBMCs from PWH and HIV-seronegative (HIV-) donors using primary T cells and monocyte derived macrophages infected in vitro or a HIV-infected T cell line (8E5) as targets +/- pooled HIV immune globulin. Both autologous and allogeneic effector cells were evaluated and the phenotype of degranulating NK cells was assessed by immunophenotyping.

Results: NK cells from PWH exhibited reduced ADCC activity against both HIV+ T cells and macrophages (p<0.001 and 0.01, respectively) as compared to NK cells from HIV- donors. NK cell degranulation in response to HIV targets was comparable but more consistent when allogeneic NK cells were used as effectors as compared to autologous cells. NK cells from PWH and HIV- donors expressing the inhibitory receptor KIR3DL2 exhibited significantly higher ADCC-mediated degranulation against both HIV-infected macrophages and T cells compared to the total NK population (p<0.0001 for all groups). KIR3DL2+ NK cells also produced more inflammatory cytokines (TNF) compared to KIR3DL2- cells (p=0.0005). Despite being present at higher proportions in PWH, adaptive NK cells (either NKG2C+CD57+ or FcRγ- CD56dim NK cells) did not show higher ADCC activity against HIV targets than total NK cells.

Conclusion: The KIR3DL2+ NK cell subset is highly ADCC competent against relevant HIV-infected cell types and may be a promising candidate for anti-HIV immunotherapeutic interventions especially in an allogeneic setting.