Effect of Recombinant Cytokines on the Expression of Natural Killer Cell Receptors from Patients with TB or/and HIV Infection

BACKGROUND: NK cells express several specialized receptors through which they recognize and discriminate virally-infected/tumor cells efficiently from healthy cells and kill them. This ability to lyse is regulated by an array of inhibitory or activating receptors. The present study investigated the frequency of various NK receptors expressed by NK cell subsets from HIV-infected TB patients. The effect of IL-15+IL-12 stimulation on the expression of NK receptors was also studied. METHODOLOGY/PRINCIPAL FINDINGS: The study included 15 individuals each from normal healthy subjects, pulmonary tuberculosis patients, HIV-infected individuals and patients with HIV and tuberculosis co-infection. The expression of NK cell receptors was analyzed on two NK cell subsets within the peripheral blood: CD16+CD3- and CD56+CD3- using flow cytometry. The expression of inhibitory receptors (CD158a, CD158b, KIRp70, CD85j and NKG2A) on NK subsets was increased in HIV, when compared to NHS. But the response in HIV-TB was not uniform. Stimulation with IL-15+IL-12 dropped (p<0.05) the expression of CD85j and NKG2A in HIV. The basal expression of natural cytotoxicity receptors (NKp30 and NKp46) on NK cell subsets was lowered (p<0.05) in HIV and HIV-TB as compared to NHS. However, the expression of NKp44 and NKG2D was elevated in HIV. Enhanced NKp46 and NKG2D expression was observed in HIV with IL-15+IL-12 stimulation. The coreceptor NKp80 was found to be expressed in higher numbers on NK subsets from HIV compared to NHS, which elevated with IL-15+IL-12 stimulation. The expression of NK receptors and response to stimulation was primarily on CD56+CD3- subset. CONCLUSIONS/SIGNIFICANCE: IL-15+IL-12 has an immunomodulatory effect on NK cell subsets from HIV-infected individuals viz down-regulation of iNKRs, elevation of activatory receptors NKp46 and NKG2D, and induction of coreceptor NKp80. IL-15+IL-12 is not likely to be of value when co-infected with TB probably due to the influence of tuberculosis

Expression of NKp46.

<p>Effect of IL-15+IL-12 on the NKp46 expression from four different groups obtained from 15 individuals. Data for CD16+CD3− and CD56+CD3− subpopulation are presented as median ± IQR. Statistical comparisons between NHS and other groups were performed and the significant values (<i>p</i><0.05) are shown as *. Statistical significance (<i>p</i><0.05) between basal and IL-15+ IL-12 stimulation were represented by #.</p

Expression of inhibitory NK receptor NKG2A.

<p>NKG2A expression at basal and IL-15+IL-12 stimulation on CD16+CD3− and CD56+CD3− cells from different groups is shown. Data are given as median ± IQR from 15 individuals in each group. Statistical comparisons between NHS and other groups were performed and the significant values (<i>p</i><0.05) are denoted by *. Statistical analysis between basal and IL-15+ IL-12 stimulation were also carried out and the significant values a(<i>p</i><0.05) re showed as #.</p

Expression of inhibitory NK receptor CD85j.

<p>The CD85j expression on CD16+CD3− and CD56+CD3− cells from different groups in the presence/absence of IL-15+IL-12 stimulation is depicted here. Data are given as median ± IQR from 15 individuals each. Statistical comparisons between NHS and other groups were performed and the significant values (<i>p</i><0.05) are shown as *. Statistical significance (<i>p</i><0.05) between basal and IL-15+ IL-12 stimulation were represented by #.</p

Expression of coreceptor NKp80 on NK cells.

<p>The expression of coreceptor NKpp80 at basal and after IL-15+IL-12 stimulation from different groups is shown. Data are given as median ± IQR from 15 individuals in each group. Statistical comparisons between NHS and other groups were performed and the significant values (<i>p</i><0.05) are shown as *. Statistical significance (<i>p</i><0.05) between basal and IL-15+ IL-12 stimulation were represented by #.</p

Expression of activatory NK receptor NKG2D.

<p>NKG2D expression on CD16+CD3− and CD56+CD3− cells from different groups in the presence/absence of IL-15+IL-12 stimulation is depicted here. Data are given as median ± IQR from 15 individuals each. Statistical comparisons between NHS and other groups were performed and the significant values (<i>p</i><0.05) are denoted by *. Statistical analysis between basal and IL-15+ IL-12 stimulation were also carried out and the significant values a(<i>p</i><0.05) re showed as #.</p