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331 Increased Natural Killer Activity in HIV-1 Exposed but Noninfected Individuals among Vietnamese Intravascular Drug Users
D. Scott-Algara*1, P. Versmisse1, A. David1, L. T. Tram2, N. V. Ngai3, I. Theodorou3, T. X. Lien2, F. Barré-Sinoussi1, and G. Pancino1
1Inst. Pasteur, Paris, France; 2Inst. Pasteur, Hosp. Binh Trieu, Ho Chi Minh City, Vietnam; and 3Hosp. Pitié-Salpêtrière, Paris, France
Background: Most studies on the resistance to infection HIV-1 in exposed noninfected individuals (ENI) have been focused on specific immune responses against HIV. However, innate immunity could play a role in natural protection against HIV infection. We addressed this question by studying the function of a component of innate response, the NK cells, in a cohort of ENI intravascular drug users (IVDU) in Ho Chi Minh City, Vietnam.
Methods: 27 IVDU ENI and 15 low risk nonexposed-noninfected donors (NENI) were studied. All individuals were HIV negative as tested by PCR and serology. PBMC were isolated and NK cell lytic activity against K-562 and Daudi cell lines was assessed. Production of cytokines by NK cells was evaluated by intracellular staining and cytometry analyses. To analyze specific cytotoxic activity against HIV-infected cells, allogeneic CD4+ cells from Vietnamese donors were infected with a local primary isolate and used as target cells in lytic assays. Moreover, ADCC function against HIV-infected target cells was tested in the presence of autologous plasma. The statistical test used to compared the 2 groups were Student’s t-test and Fisher’s exact test.
Results: NK cell lytic activities against both K-562 and Daudi cell lines were significantly higher in ENI compared to NENI (effector/target cell ratio 50:1; 25:1, and 12:5; p < 0.001). Accordingly, the proportions of NK cells stained by IFN-gamma, TNF-alpha, RANTES, MIP1-alpha and beta, were higher in ENI than in NENI (p < 0.01). ADCC activity against HIV infected cells were detected in 2 out of the 25 ENI and in no NENI.
Conclusions: Increased NK cell cytotoxicity was observed in ENI when compared to low-risk donors. The increase of NK activity in ENI was also evidenced by increased production of cytokines and chemokines. These data suggest that activated NK cells may contributed to natural protection against HIV-1 in Vietnamese IVDU ENI either through secretion of antiviral cytokines and/or by lysis of infected cells.
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