Natural killer cells in cross-regulation of IL-12 by IL-10 inLeishmaniaantigen-stimulated blood donor cells

Abstract

We have previously shown that natural killer (NK) cells play a role in protection against leishmaniasis. Furthermore, we have shown that NK cells in mononuclear cells derived from unexposed donors are induced to proliferate in vitro in response to leishmanial antigens. Since interleukin (IL)-12, a strong inducer of NK cells, acts on the early events in NK cells and T-cells, and is considered as an adjuvant for use in a potential antileishmaniasis antigen, we wished to investigate how this cytokine influences the in vitro Leishmania induced proliferative and cytokine response in healthy donors. We demonstrate that in an innate response to Leishmania antigen involving NK cells, a critical level of IL-12 is required to induce interferon (IFN)-gamma secretion below which, IL-10 is released in amounts which apparently inhibit IFN-gamma secretion and cellular proliferation. However, at higher IL-12 levels, there is simultaneous secretion of IFN-gamma and IL-10 as well as proliferation of cells. In a similar vein, exogenous IL-10 in turn inhibited IFN-gamma secretion as well as proliferation when used at low/medium concentrations, but at high concentrations this effect was abolished and replaced by the simultaneous detection of IFN-gamma, IL-10 and proliferation. The contribution of NK cells in cross regulation of these two very important immuneregulatory cytokines and the effect of exogenous IL-12 in a Leishmania driven response are discussed.

ALeishmaniaHomologue of Receptors for Activated C‐Kinase (LACK) Induces Both Interferon‐γ and Interleukin‐10 in Natural Killer Cells of Healthy Blood Donors

“…Inactivation of MHC class II would result in lowered levels of CD4 ϩ as well as CD16/56 ϩ cells. This model is consistent with our finding that CD16/56 ϩ cells alone cannot be activated by FtLeish Ag but require the presence of other cell types to be preferentially induced to proliferate and secrete cytokines [18]. Our data also show that, in the presence of plastic-adherent cells and in the absence of CD4 ϩ cells, NK cells can secrete high levels of IFN-g in response to LACK stimulation.…”

“…We have elsewhere shown that NK cells alone cannot be stimulated to proliferate or to secrete IFN-g in our Ft-Leish system [18]. Thus, in the present study, we evaluated the capacity of LACK (a candidate prominent component of the Ft-Leish response in healthy donors) to be stimulatory to NK cells in the presence of adherent cells.…”

NK cell compartment in patients with coronary heart disease

“…Similarly, production of IL-10 by monocytes is elevated during the infection with Chlamydia pneumoniae [29]. IL-10 is a cytokine which directly influences NK cells quenching their cytotoxic activity [30]. IL-10 counteracts IL-2 secretion, which results in decrease of NK cell function [31,32].…”

Phase II Trial of Systemic Recombinant Interleukin-2 in the Treatment of Refractory Nasopharyngeal Carcinoma

“…A low basal level and an elevated circulating IL-6 after IL-2 therapy have been regarded as good indicators of predicting an anticancer response [19]. In contrast, IL-10 is regarded as a potent immunosuppressive factor, which involves in the inhibition of interferon-γ secretion and T cell proliferation after antigen stimulation [20]and plays an important role in the stress-induced immunosuppression [21]. IL-10 is causally involved in dampening the inflammatory response induced by IL-2 [22].…”