Research Article: Changes to the Natural Killer Cell Repertoire after Therapeutic Hepatitis B DNA Vaccination

Date Published: January 18, 2010

Publisher: Public Library of Science

Author(s): Daniel Scott-Algara, Maryline Mancini-Bourgine, Hélène Fontaine, Stanislas Pol, Marie-Louise Michel, T. Mark Doherty.

Abstract: Improvements to the outcome of adaptive immune responses could be achieved by inducing specific natural killer (NK) cell subsets which can cooperate with dendritic cells to select efficient T cell responses. We previously reported the induction or reactivation of T cell responses in chronic hepatitis B patients vaccinated with a DNA encoding hepatitis B envelope proteins during a phase I clinical trial.

Partial Text: Natural Killer (NK) cells have recently been identified as crucial actors of innate host immunity in response to a variety of pathological challenges [1]. Their role in controlling pathogenesis induced by infection is dual and can occur through both cytokine/ chemokine secretion and antibody dependent or natural cytotoxic activity toward infected target cells. Human NK cells represent 5–20% of all circulating lymphocytes and based upon their cell surface density of CD56, two distinct populations of human NK have been identified [2]. Most of human NK cells have low-density expression of CD56 (CD56dim) and are the more cytotoxic subset. In contrast, CD56bright subset that represents 10% of the NK cells has the capacity to produce abundant cytokines. NK cells also express several families of receptors including both inhibitory and activating receptors [1]. These receptors, by delivering inhibitory signals to NK cells, can prevent unwanted responses to normal cells that express a complete set of self-MHC molecules. Several studies reported distinct NK cell repertoire and/or NK cell ligand expression during viral infections and their correlation in either the control or the resistance against infections [3]. The cross talk between NK and antigen presenting cells influences efficiency of adaptive immune responses against virus, thus constituting a major link between innate and adaptive immune responses [3].

Priming of protective T cell responses has been shown in different models of virus infection to be deeply affected by the cross-talk between NK and DCs, where NK cells play a key regulatory function essential for DC maturation and subsequent T cell priming [19]. The activation of NK cells during therapeutic intervention may therefore be important to the clearance of infection. Here, we have demonstrated that the DNA-based vaccination of HBV chronic carriers not only activated detectable HBV-specific T cells in the periphery but also induced an increase in a particular subset of NK cells. The NK cell increase was correlated with the number of HBV-specific IFN-γ-secreting T cells activated by the DNA vaccine.



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