Publications & Reports

Virologically Suppressed HIV Patients Show Activation of NK Cells and Persistent Innate Immune Activation.

Lichtfuss GF, Cheng WJ, Farsakoglu Y, Paukovics G, Rajasuriar R, Velayudham P, Kramski M, Hearps AC, Cameron PU, Lewin SR, Crowe SM, Jaworowski A
Centre for Virology, Burnet Institute, Melbourne, Victoria 3004, Australia;


FcRgamma is an ITAM-containing adaptor required for CD16 signaling and function in NK cells. We have previously shown that NK cells from HIV patients receiving combination antiretroviral therapy (cART) have decreased FcRgamma expression, but the factors causing this are unknown.

We conducted a cross-sectional study of cART-naive viremic patients (ART(-)), virologically suppressed patients receiving cART (ART(+)), and HIV-uninfected controls. CD8(+) T cells were activated, as assessed by CD38(+)HLA-DR(+) expression, in ART(-) patients (p < 0.0001), which was significantly reduced in ART(+) patients (p = 0.0005). In contrast, CD38(+)HLA-DR(+) NK cells were elevated in ART(-) patients (p = 0.0001) but did not decrease in ART(+) patients (p = 0.88). NK cells from both ART(-) and ART(+) patients showed high levels of spontaneous degranulation in ex vivo whole blood assays as well as decreased CD16 expression (p = 0.0001 and p = 0.0025, respectively), FcRgamma mRNA (p < 0.0001 for both groups), FcRgamma protein expression (p = 0.0016 and p < 0.0001, respectively), and CD16-dependent Syk phosphorylation (p = 0.0001 and p = 0.003, respectively).

HIV-infected subjects showed alterations in NK activation, degranulation, CD16 expression and signaling, and elevated plasma markers of inflammation and macrophage activation, that is, neopterin and sCD14, which remained elevated in ART(+) patients. Alterations in NK cell measures did not correlate with viral load or CD4 counts. These data show that in HIV patients who achieve viral suppression following cART, NK cell activation persists. This suggests that NK cells respond to factors different from those driving T cell activation, but which are associated with inflammation in HIV patients.

This work was supported in part by National Health and Medical Research Council Project Grant 543137. S.R.L. is supported by a National Health and Medical Research Council Practitioner Fellowship and by The Alfred Foundation. S.M.C. is supported by a National Health and Medical Research Council Principal Research Fellowship. The authors gratefully acknowledge the contribution to this work of the Victorian Operational Infrastructure Support Program.

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  • Journal: Journal of Immunology
  • Published: 27/06/2012
  • Volume: 189
  • Issue: 3
  • Pagination: 1491-1499


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