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Natural killer (NK) cells are a component of innate immunity against viral infections through their rapid cytotoxic activity and cytokine production. However, intra-hepatic NK cells' ability to respond to virus is still mostly unknown. Our results show that the synthetic dsRNA polyinosinic-polycytidylic acid (poly I:C), a mimic of a common product of viral infections, activates NK cells directly in the context of cytokines found in the liver, i.e.: poly I:C plus inflammatory cytokines (IL-18, IL-12, and IL-2) induced NK cell IFN-γ production and TRAIL expression, and anti-inflammatory cytokines (TGF-β and IL-10) inhibit NK cell IFN-γ production. Neutralization of IFN-γ blocks poly I:C plus inflammatory cytokines-induced NK cell TRAIL expression, suggesting that IFN-γ is an autocrine differentiation factor for these cells. A better understanding of the intra-hepatic NK cell activation against viral infection may help in the design of therapies and vaccines for the control of viral hepatitis., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Dendritic cells (DC) are highly specialized antigen presenting cells that play critical roles as instigators and regulators of immune responses including B cell function, antibody synthesis and isotype switch. In this study, we compared immunotherapeutic effect of IL-10-treated DC (IL-10-DC) via both intraperitoneal (i.p.) and subcutaneous (s.c.) delivery in rats with incipient experimental autoimmune myasthenia gravis (EAMG). Spleen DC were isolated from onset of EAMG on day 39 post-immunization, exposed in vitro to IL-10, and then injected into incipient EAMG at dose of 1 x 10(6) cells/rat on day 5 after immunization. Intraperitoneal administration of IL-10-DC suppressed clinical scores, anti-acetylcholine receptors (AChR) antibody secreting cells, antigen-specific IL-10/IFN-gamma production and T cell proliferation compared to control EAMG rats. Importantly, IL-10-DC, if given by s.c. route, failed to ameliorate clinical sign of EAMG. Simultaneously, T cell proliferation, anti-AChR antibody secreting cells and IL-10/IFN-gamma production had no alteration, as compared to control EAMG rats. Both in vitro and in vivo experiments showed that treatment of IL-10 inhibited the migration of DC toward MIP-3beta and lymph node, indicating that in vitro manipulation of DC with IL-10 alters the migration of DC that influences the therapeutic effect in the treatment of autoimmune diseases. In MG patients, neither the improvement of clinical symptom nor the alteration of immunological parameter was observed through s.c. delivery of IL-10-DC, suggesting the limitation of IL-10-DC in the treatment of MG patients.

In the present report, we have evaluated and compared the modulatory effect of the cytokine interleukin (IL)-10 expressed via viral vector or plasmid DNA on viral antigen-induced cutaneous inflammatory lesions. Our data demonstrate the superior potency of both recombinant vaccinia virus and herpes simplex virus IL-10 expression vectors after single intramuscular administration, but the effects were only short term and only functioned in animals lacking immunity to the viral vectors used for modulation. In contrast, modulatory effects achieved by plasmid DNA expressing IL-10 were delayed in onset and milder in effect but were far more persistent than those achieved by viral vectors. Moreover, plasmid DNA expressing IL-10 provided effective modulation when given repeatedly to animals. Our data also showed that IL-10 gene delivery resulted in a systemic and durable modulatory effect while the effect caused by a single IL-10 protein treatment was transient and confined to the injected site. Our results imply that the viral vector system is superior for obtaining short-term effects, whereas the plasmid DNA approach represents a better strategy to achieve gene therapy to modulate chronic inflammatory lesions., (Copyright 1999 Academic Press.)

The role of the interplay of interleukin-2 (IL-2) and interleukin-10 (IL-10) in responses of human peripheral blood B cells stimulated by ligation of antigen receptors was examined in detail. Highly purified peripheral blood B cells from normal human individuals were cultured with Staphylococcus aureus Cowan I (SA) in the presence or absence of IL-10 and IL-2. Although IL-10 alone could modestly induce Ig production by SA-activated B cells, IL-10 markedly enhanced the Ig production in synergism with IL-2. This synergistic effect between IL-2 and IL-10 was completely abrogated by addition of either anti-CD25 mAb or anti-IL-10 mAb, indicating signals through high-affinity IL-2 receptors are involved in the synergism. In fact, IL-10 upregulated the expression of alpha-chain of IL-2 receptors (CD25) on B cells stimulated by SA alone or SA + IL-2 for 72 hr. However, such upregulation of CD25 expression did not result in significant enhancement of subsequent responses of the activated B cells to IL-2. Of note, during the initial activation phase of B cells, IL-2 was much more effective than IL-10 in enhancing the subsequent responses to either IL-2 or IL-10. By contrast, IL-10 was much more effective than IL-2 in supporting the maturation of B cells following the initial activation. Finally, the synergy between IL-2 and IL-10 was not observed in the initial activation phase, but in the subsequent maturation phase of activated B cells. These results indicate that IL-10 and IL-2 synergistically enhance Ig production of SA-activated B cells in a mechanism which is different from the upregulation of IL-2 receptors. Moreover, the data emphasize the importance of the interplay of IL-2 and IL-10 in determining the outcome of humoral immune responses.