Abstract
BackgroundNK 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 FindingsThe 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/SignificanceIL-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.
Highlights
Natural Killer (NK) cells represent a highly specialized lymphoid population that lack antigen specific receptors, but can lyse tumor and virus-infected cells, without prior sensitization [1]
Expression of Inhibitory NK Receptors The proportion of various inhibitory NK receptors (iNKRs)- CD158a, CD158b, KIRp70, CD85j and NKG2A expressed by NK cell subsets were measured and are as follows: CD158a, CD158b and KIRp70
Representative flow cytometric dot plot of CD16+ cells and CD56+ cells (Fig. 1a) and the histograms showing the expression of CD158a from NK cell subsets (CD16+CD32 and CD56+CD32) among four different groups (Fig. 1b) are presented
Summary
Natural Killer (NK) cells represent a highly specialized lymphoid population that lack antigen specific receptors, but can lyse tumor and virus-infected cells, without prior sensitization [1]. They commonly express a variety of nonexclusive phenotypic markers such as CD16, CD56, CD57, and to some extent CD8 [2]. 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 effect of IL-15+IL-12 stimulation on the expression of NK receptors was studied
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