Background: Innate immunity might contribute to protection from HIV-1 infection. We addressed this question by studying NK cell function in a population of Vietnamese HIV-1 exposed intra-vascular drug users (IDU) who, despite more than 10 years of high-risk behaviours, remain apparently uninfected (EU).

Methods: Thirty-seven (37) EU IDU, 10 IDU who seroconverted during the follow-up and 28 unexposed controls were included in the study. NK cell activity was assessed using PBMC as effectors and K562 or Daudi cell lines or allogenic HIV-1 infected CD4⁺ cells as targets. Cytokine and β-chemokine production by NK cells was evaluated by intracellular staining.

Results: NK cell activities against K562 and Daudi cell lines were significantly increased in EU IDU (●) compared to either unexposed controls (□) or seroconverters before (▲) or after (○) seroconversion (p < 0.001).

Higher proportions of NK cells producing cytokines and β-chemokines were found in EU IDU compared to seroconverters or unexposed controls after in vitro activation as well as without stimulation.

CYTOKINE	GROUP#	UNSTIMULATED		K562 STIMULATED
		Mean ± SD¤	P*	Mean ± SD¤	P*
IFN-γ	EU IDU	13.1 ± 6.22		26.0 ± 9.65
	CONTROL	1.02 ± 0.97	< 0.005	17.5 ± 5.78	0.28
	SEROCONVERTER B.S	0.24 ± 0.27	< 0.005	2.0 ± 1.58	< 0.005
	SEROCONVERTER A.S	0.10 ± 0.11	< 0.005	0.07 ± 0.08	< 0.005
TNF-α	EU IDU	10.94 ± 2.42		32.0 ± 10.6
	CONTROL	2.58 ± 1.41	< 0.05	18.0 ± 6.38	< 0.05
	SEROCONVERTER B.S	0.33 ± 0.38	< 0.005	2.16 ± 2.22	< 0.005
	SEROCONVERTER A.S	0.15 ±0.19	< 0.005	0.33 ± 0.54	< 0.005
MIP 1-α (CCL-3)	EU IDU	9.82 ± 3.63		36.51 ± 9.43
	CONTROL	0.68 ± 0.68	< 0.002	20.67 ± 4.89	< 0.01
	SEROCONVERTER B.S	0.11 ± 0.09	< 0.005	1.75 ± 1.61	< 0.001
	SEROCONVERTER A.S	0.10 ± 0.09	< 0.005	1.15 ± 2.38	< 0.002
MIP 1-β (CCL-4)	EU IDU	9.64 ± 3.91		31.83 ± 8.85
	CONTROL	2.69 ± 2.03	< 0.05	16.50 ± 5.01	< 0.05
	SEROCONVERTER B.S	1.45 ± 1.67	< 0.01	1.33 ± 1.22	< 0.005
	SEROCONVERTER A.S	0.15 ± 0.11	< 0.005	0.95 ± 1.99	< 0.005
RANTES (CCL-5)	EU IDU	17.41 ± 7.57		36.33 ± 14.04
	CONTROL	6.05 ± 2.58	< 0.03	20.50 ± 6.72	< 0.01
	SEROCONVERTER B.S	1.53 ± 1.21	< 0.005	2.33 ± 2.07	< 0.005
	SEROCONVERTER A.S	0.16 ± 0.67	< 0.005	0.33 ± 0.35	< 0.005

 

Conclusions: Increased NK cell cytotoxic and secretory activities in the EU IDU may result from exposure to multiple infections together with allogenic stimulation in this population. The enhancement of NK activity in EU IDU compared to IDU who became HIV-1 infected supports the possibility that NK cells may contribute to the resistance to HIV-1 infection.