12th Annual Conference of the British HIV Association 29 March–1 April 2006, Brighton, UK

SWITCH IN C-TYPE LECTIN RECEPTOR PHENOTYPE FROM NKG2A TO NKG2C IN HIV-1 INFECTION

HIV Med 2006; 7(Suppl. 1):6 (abstract no. O23)

Christopher M Mela¹, Catherine T Burton¹, Nesrina Imami¹, Mark Bower², Mark Nelson², Alan Steel², Brian G Gazzard², Frances M Gotch¹ and Martin R Goodier^1
1 Imperial College, London, ² Chelsea & Westminster Hospital, London, UK

AIMS: HIV-1 infection is characterised by an increase in inhibitory receptors and loss of activating receptors on natural killer (NK) cells, resulting in loss of NK cell activity. Paradoxically, the proportion of NK cells bearing inhibitory NKG2A decreases during infection but CD94 co-receptor remains constant. Here we test whether another receptor, NKG2C, is preferentially expressed in HIV-1 infection and if this corresponds to dysregulation of other NK receptors.

METHODS: We have studied HIV-1-positive treatment-naïve (TN) individuals (n=13), HIV-1-positive individuals receiving successful antiretroviral therapy (ART) for a minimum of 1 year without interruption (n=10) and a group of 10 age-matched healthy control (HC) individuals. Flow cytometry was used to study the expression of killer immunoglobulin-like receptors (KIRs), natural cytotoxicity receptors (NCRs) and C-type lectin receptors to define expanded populations of NK cells. In vitro assays of secretory functions and cytotoxicity were performed. Mann-Whitney U-test and Wilcoxon signed rank test were used for analyses.

RESULTS: We have shown highly significant differences in the expression of NKG2C between HC (5% of CD94+ NK cells) and HIV-1-positive TN individuals (37% of CD94+ NK cells) (P<0.0001). We also observe significantly altered expression of KIR and NCR between these subsets of NK cells. These NK cells from HIV-1-positive individuals express perforin and exhibit cytotoxicity and so are potentially functional.

CONCLUSION: We demonstrate a dramatic switch from NKG2A (inhibitory) to functional NKG2C (activatory) receptor-expressing NK cells in HIV-1-infected individuals with concurrent redistribution of NCR and KIR. This emergence of NKG2C+ NK cells may have consequences for the recognition and survival of infected CD4+ T cells in HIV-1-positive individuals.

2006-03-29
O23

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