Impaired Natural Killer Cell Activity Associates with Increased Susceptibility to Inflammation Induced by Herpesvirus Infection in Patients with Nickel Hypersensitivity

Abstract

Nickel (Ni) is one of the most common causes of allergic contact dermatitis (ACD) and the number one allergen in the frequency of positive patch test reactions. The cellular basis of ACD is the lack of specialized T cells with regulatory function allowing for the expansion of Ni specific cytotoxic CD8+ T cells. However, Ni also exerts a number of not yet fully understood activities on cells belonging to the immune system. To this regard, an immunosuppressive activity of Ni on natural killer (NK) cells has been repeatedly suggested both in animal models and humans. Here we demonstrate that NK activity of Ni intolerant patients was significantly lower than observed in controls. Moreover, the addition of Ni sulphate to cultures of peripheral blood lymphocytes (PBL) obtained by Ni allergic patients, further depressed the NK cell activity. Finally, according to the key role exerted by NK cells in containing viral infections, we found an increased frequency of Herpesvirus 1 (HSV-1) recurrence among patients with Ni allergy. In conclusion, our results indicate that Ni allergic patients may present reduced NK cell response, this resulting in turn in increased susceptibility to viral infections. Patch testing should be considered in individuals affected by unexplained recurrences of HSV-1 infection.