Enhanced natural killer cell activity is found in exposed uninfected recipients of hepatitis C-contaminated blood

Abstract

<jats:title>Summary</jats:title><jats:p>A minority of injecting drug users, termed exposed uninfected, are resistant to hepatitis C (<jats:styled-content style="fixed-case">HCV</jats:styled-content>) infection despite repeated low‐dose exposures. We identify for the first time a cohort of blood recipients who remained uninfected despite large‐dose exposure to <jats:styled-content style="fixed-case">HCV</jats:styled-content>‐contaminated blood and characterize immune factors that may confer protection. Of 1340 blood recipients from the English Look Back database who were transfused <jats:styled-content style="fixed-case">HCV</jats:styled-content>‐contaminated blood, we identified 8 who remained uninfected. In these 8 exposed uninfecteds, we characterized their natural killer (<jats:styled-content style="fixed-case">NK</jats:styled-content>) cell populations and <jats:styled-content style="fixed-case">HCV</jats:styled-content>‐specific T‐cell responses. Findings were compared with 10 spontaneous resolvers of <jats:styled-content style="fixed-case">HCV</jats:styled-content> infection, 10 patients with chronic <jats:styled-content style="fixed-case">HCV</jats:styled-content> infection and 10 healthy controls. Exposed uninfecteds had significantly greater numbers of <jats:styled-content style="fixed-case">NK</jats:styled-content> cells with the activating receptor <jats:styled-content style="fixed-case">NK</jats:styled-content>p30+ on <jats:styled-content style="fixed-case">CD</jats:styled-content>56<jats:sup>bright</jats:sup> and <jats:styled-content style="fixed-case">CD</jats:styled-content>56<jats:sup>dim</jats:sup> subsets compared with other groups (<jats:italic>P</jats:italic> &lt; .05). Following interleukin‐2 activation, <jats:styled-content style="fixed-case">NK</jats:styled-content> cells of exposed uninfecteds had enhanced cytotoxicity that positively correlated with <jats:styled-content style="fixed-case">NK</jats:styled-content>p30 expression (<jats:italic>P</jats:italic> = .02). Differences in <jats:styled-content style="fixed-case">NK</jats:styled-content>p80 and <jats:styled-content style="fixed-case">KIR</jats:styled-content>2<jats:styled-content style="fixed-case">DL</jats:styled-content>3 expression were also observed. <jats:styled-content style="fixed-case">HCV</jats:styled-content>‐specific T‐cell responses were observed in some exposed uninfecteds but of low amplitude. Exposure without infection following transfusion of <jats:styled-content style="fixed-case">HCV</jats:styled-content>‐contaminated blood is a very rare phenomenon and suggests a high level of resistance to infection. Enhanced <jats:styled-content style="fixed-case">NK</jats:styled-content> cell activation and killing, with weak <jats:styled-content style="fixed-case">HCV</jats:styled-content>‐specific T‐cell responses, were observed many years after exposure in uninfected recipients and may contribute to protection from <jats:styled-content style="fixed-case">HCV</jats:styled-content> acquisition, although additional protective factors are being sought in this important cohort.</jats:p>