Background:  Enhanced NK cell cytotoxic and cytokine production potential was evidenced in Vietnamese intravascular drug users (IDU), who remained uninfected by HIV despite long-time high-risk exposure (EU). We evaluated the expression of NK cell markers that may characterize the activated status of NK cells in EU, as compared to unexposed HIV^– or HIV⁺ Vietnamese individuals.

Methods:  The size of NK cell subsets expressing NK markers was evaluated by flow cytometry in 18 EU and 19 unexposed Vietnamese blood donors. Phenotypic markers analyzed included available KIR, CD94/NKG2, ILT2, NKG2D, NCR, NKRP1, CD69, and CD25. NK cell markers associated to NK cytolytic or cytokine function were also analyzed by real-time PCR analysis using specific primers discriminating activating and inhibitory NKR transcripts expression levels in 23 EU and 21 unexposed individuals and analyzed by unpaired t-test.

Results:  No significant increase in percentage of NK cells was observed in EU (mean ± SEM = 18.8 ± 2.9) as compared to unexposed Vietnamese (19.06 ± 2.9), while HIV⁺ Vietnamese exhibited lowered percentages of NK cells. Five cases of NK cell expansion (NK > 30%) were characterized both in 3 EU and 2 unexposed Vietnamese donors. Cell surface mean expression of NCR or NKG2D activating receptors was low in EU. Size of NK cell subsets bearing activating receptors (KIR3DS1, KIR2DS4, CD161, CD69) and inhibitory (CD85j, KIR2DL3, KIR2DL1) are abnormally elevated in EU. Enhanced activating KIR3DS1/inhibitory KIR3LDL1 ratios characterize oligoclonal KIR3DS1 expansions in 3 EU.

Conclusions:  Analysis of the NK cell repertoire of EU who are protected from HIV infection reveals specific features that may confer activated NK cells with better protective capacities in controlling HIV infection. Although the sample of protected individuals is too small to derive consistent NK receptor patterns of expressed genes associated to EU, altered enhanced representation of some KIR, CD69, CD161, and CD85j is observed in some EU. In particular, as shown previously in relation to AIDS or hepatitis C, selective expansion of KIR3DS1⁺ or KIR2DL3⁺ NK cell subsets, detected here by real-time PCR, may represent an advantage for NK cells in better resolving HIV infection in some EU. The functional relevance of enhanced expression of CD85j, CD161, and KIR expression needs to be further assessed.

Keywords: NK cells; Innate immunity; anti HIV immune response