title: Changes in Natural Killer cell activation and function during primary HIV-1 Infection.
abstract: BACKGROUND
  Recent reports suggest that Natural Killer (NK) cells may modulate pathogenesis of primary HIV-1 infection. However, HIV dysregulates NK-cell responses. We dissected this bi-directional relationship to understand how HIV impacts NK-cell responses during primary HIV-1 infection.
  
  
  RESULTS
  Paired samples from 41 high-risk, initially HIV-uninfected CAPRISA004 participants were analysed prior to HIV acquisition, and during viraemic primary HIV-1 infection. At the time of sampling post-infection five women were seronegative, 11 women were serodiscordant, and 25 women were seropositive by HIV-1 rapid immunoassay. Flow cytometry was used to measure NK and T-cell activation, NK-cell receptor expression, cytotoxic and cytokine-secretory functions, and trafficking marker expression (CCR7, α(4)β(7)). Non-parametric statistical tests were used. Both NK cells and T-cells were significantly activated following HIV acquisition (p = 0.03 and p<0.0001, respectively), but correlation between NK-cell and T-cell activation was uncoupled following infection (pre-infection r = 0.68;p<0.0001; post-infection, during primary infection r = 0.074;p = 0.09). Nonetheless, during primary infection NK-cell and T-cell activation correlated with HIV viral load (r = 0.32'p = 0.04 and r = 0.35;p = 0.02, respectively). The frequency of Killer Immunoglobulin-like Receptor-expressing (KIR(pos)) NK cells increased following HIV acquisition (p = 0.006), and KIR(pos) NK cells were less activated than KIR(neg) NK cells amongst individuals sampled while seronegative or serodiscordant (p = 0.001;p<0.0001 respectively). During HIV-1 infection, cytotoxic NK cell responses evaluated after IL-2 stimulation alone, or after co-culture with 721 cells, were impaired (p = 0.006 and p = 0.002, respectively). However, NK-cell IFN-y secretory function was not significantly altered. The frequency of CCR7+ NK cells was elevated during primary infection, particularly at early time-points (p<0.0001).
  
  
  CONCLUSIONS
  Analyses of immune cells before and after HIV infection revealed an increase in both NK-cell activation and KIR expression, but reduced cytotoxicity during acute infection. The increase in frequency of NK cells able to traffic to lymph nodes following HIV infection suggests that these cells may play a role in events in secondary lymphoid tissue.
authors: CAPRISA - Centre for the AIDS Programme of Research in South Africa, Doris Duke Medical Research Institute, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa.
authors: Vivek
authors: V
authors: Naranbhai
authors: Marcus
authors: M
authors: Altfeld
authors: Salim S Abdool
authors: SS
authors: Karim
authors: Thumbi
authors: T
authors: Ndung'u
authors: Quarraisha Abdool
authors: QA
authors: Karim
authors: William H
authors: WH
authors: Carr
mesh_terms: D000293:Adolescent; D000328:Adult; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000276:immunology* / Q000503:physiopathology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D018655:Lymphocyte Count; D008221:Lymphoid Tissue / Q000276:immunology / Q000473:pathology; D008297:Male; D054340:Receptors, KIR / Q000276:immunology; D016201:Receptors, Lymphocyte Homing / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology; D019562:Viral Load / Q000276:immunology; D055815:Young Adult
chemical_list: D054340:Receptors, KIR; D016201:Receptors, Lymphocyte Homing