Статьи

Types of NK Сells Responses to IFN-α in patients with Frequently Recurrent Herpes Simplex

European Academy of Allergy and Clinical Immunology - World Allergy Organization 2013, Milan, Italy

Poster Session 28

Innate and adaptive immune responses

Types of NK Сells Responses to IFN-α in patients with Frequently Recurrent Herpes Simplex
Karsonova A1, 3, Shulzhenko A2 , Karaulov V1

1Department of Clinical Immunology and Allergology, I.M. Sechenov First Moscow State Medical University, Moscow, Russia; 2Department of Allergy and Immunotherapy, National Research Center “Institute of Immunology of the Federal Medical-Biological Agency,” Moscow, Russia; 3Laboratory of Clinical Immunology, National Research Center “Institute of Immunology of the Federal Medical-Biological Agency,” Moscow, Russia

Backgroun: NK cells, which are principal antiviral effector cells, accomplish their effector function by degranulation, i.e. by releasing cytotoxic proteins from lytic granules onto the surface of target cells. This study aimed to investigate k562-induced NK cells-degranulation and cytotoxicity under the IFN-α influence in patient with frequently recurrent herpes simplex (FRHS).

Methods: MNCs were obtained from 48 patients with FRHS and from 31 age-matched healthy donors. MNCs were incubated in presence of IFN-α2b (10, 100 and 1000 IU/ml) for 24 h. Control aliquot was incubated without IFN-α2b. After 24 h NK cells response to IFN was assessed by NK cell degranulation and NK cytotoxicity assay. Degranulation was induced by adding K562 target cells and assessed by flow cytometry with monoclonal antibodies against CD107. In order to assess NK cytotoxicity effectorMNCs were incubated 4 h with k562, labeled with carboxyfluorescein diacetate succinimidyl ester. The dead K-562 cells were stained with propidium iodide and analysed by flow cytometry.

Results: We identified a group of patients who had no significant degranulation increase in response to increasing concentration of IFN from 10 to 1000 IU/ml (marked as type B). Rest of patients had degranulation increase like donors (marked as type A). Identified groups (A and B) had principal differences in NK-cytotoxicity. During remission group A was characterized by normal non-stimulated NK-cytotoxicity and low IFN-stimulated NK-cytotoxicity. During recurrence significant difference between group A and healthy donors wasn’t observed. On the contrary, during remission group B had normal non-stimulated and normal IFN-stimulated NK-cytotoxicity. During recurrence in group B non-stimulated and IFN-stimulated NK-cytotoxicity was in 3 times lower than in healthy donors.

Conclusion: Thus, patients with FRHS are heterogeneous group and have different defects in system “IFN type I/NK cell cytotoxicity”. We identified 2 types of NK cells responses to IFN-α. In group A NK cells had low “susceptibility” to IFN-α during remission and didn’t have any defects during exacerbation, whereas group B had normal “susceptibility” to IFN-α during remission and strong immunodeficiency during exacerbation. Immunotherapeutic approaches should be based on the type of response.

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