ANTI-APOPTOTIC EFFECT OF CD95 RECEPTOR IN NA VE CD8+ T-LYMPHOCYTES IN CHILDREN WITH ACUTE INFECTIOUS MONONUCLEOSIS

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Abstract

Acute infectious mononucleosis is a widespread viral disease, which most often manifests in childhood. The development of acute infectious mononucleosis is accompanied by the change of the CD4+/CD8+ T-lymphocytes ratio and the increase of the virus-specific CD8+ cytotoxic T-lymphocytes number. One of the T-lymphocytes number regulation mechanisms is the modulation of their progenitor cells apoptosis. The death receptor CD95 takes part in the regulation of T-lymphocytes apoptosis, including naïve T-cells. We studied the effect of CD95 receptor activation on apoptosis of naïve CD4+ and naïve cytotoxic CD8+ T-lymphocytes in healthy children and children with acute infectious mononucleosis. In this study children with acute infectious mononucleosis at the age of 9 to 16 years were included. For comparison healthy children of the same age with no clinical and laboratory signs of the disease were used. Naïve CD4+ and naïve cytotoxic CD8+ T-lymphocytes were isolated by negative magnetic immunoseparation. The analysis of naïve T-cells apoptosis and the CD95 receptor surface expression density was performed by using the flow cytometry analysis. The analysis of T-cells was performed in three variants: freshly isolated naïve CD4+ T-lymphocytes and naïve cytotoxic CD8+ T-lymphocytes, and also cells after 24 hours of the cultivation with anti-CD95 monoclonal antibodies or without them. In healthy children both CD95– and CD95+ naïve CD4+ T-lymphocytes underwent apoptosis. In children with acute infectious mononucleosis CD95– naïve CD4+ T-lymphocytes lost their susceptibility to apoptosis induction. In healthy children and children with acute infectious mononucleosis CD95– naïve cytotoxic CD8+ T-lymphocytes were resistant to apoptosis in contrast to CD95+ naïve CD4+ T-lymphocytes. In healthy children CD95 receptor did not induce apoptosis of isolated naïve CD4+ T-lymphocytes and naïve cytotoxic CD8+ T-lymphocytes. In children with acute infectious mononucleosis CD95 receptor was involved in inhibition of apoptosis of naïve cytotoxic CD8+ T-lymphocytes and did not effect on the level of apoptosis of naïve CD4+ T-lymphocytes. We suggest that CD95-dependent suppression of naïve cytotoxic CD8+ T-lymphocytes apoptosis is a protective mechanism for the maintenance of a sufficient number of cytotoxic T-lymphocytes in the blood for the realization of effective antiviral immune response.

About the authors

E. N. Filatova

Blokhina Research Institute of Epidemiology and Microbiology of Federal Service on Surveillance for Consumer Rights Protection and Human Welfare, Nizhny Novgorod, Russian Federation

Author for correspondence.
Email: filatova@nniiem.ru

PhD (Biology), Leading Researcher, Laboratory of Molecular Biology and Biotechnology, Blokhina Research Institute of Epidemiology and Microbiology, Nizhny Novgorod, Russian Federation;

Russian Federation

E. V. Anisenkova

Blokhina Research Institute of Epidemiology and Microbiology of Federal Service on Surveillance for Consumer Rights Protection and Human Welfare, Nizhny Novgorod, Russian Federation

Email: fake@neicon.ru

Junior Researcher, Laboratory of Molecular Biology and Biotechnology, Blokhina Research Institute of Epidemiology and Microbiology, Nizhny Novgorod, Russian Federation;

Russian Federation

N. B. Presnyakova

Blokhina Research Institute of Epidemiology and Microbiology of Federal Service on Surveillance for Consumer Rights Protection and Human Welfare, Nizhny Novgorod, Russian Federation

Email: fake@neicon.ru

Researcher, Laboratory of Molecular Biology and Biotechnology, Blokhina Research Institute of Epidemiology and Microbiology, Nizhny Novgorod, Russian Federation;

Russian Federation

T. D. Sycheva

Nizhny Novgorod State Medical Academy, Nizhny Novgorod, Russian Federation

Email: fake@neicon.ru

Resident Physician, Department of Children Infections, Nizhny Novgorod State Medical Academy, Nizhny Novgorod, Russian Federation;

Russian Federation

E. A. Kulova

Nizhny Novgorod State Medical Academy, Nizhny Novgorod, Russian Federation

Email: fake@neicon.ru

PhD (Medicine), Assistant Professor, Nizhny Novgorod State Medical Academy, Nizhny Novgorod, Russian Federation

Russian Federation

O. V. Utkin

Blokhina Research Institute of Epidemiology and Microbiology of Federal Service on Surveillance for Consumer Rights Protection and Human Welfare, Nizhny Novgorod, Russian Federation;
Nizhny Novgorod State Medical Academy, Nizhny Novgorod, Russian Federation

Email: fake@neicon.ru

PhD (Biology), Head of the Laboratory of Molecular Biology and Biotechnology, Blokhina Research Institute of Epidemiology and Microbiology;
Associate Professor, Department of Microbiology and Immunology, Nizhny Novgorod State Medical Academy, Nizhny Novgorod, Russian Federation.

Russian Federation

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Copyright (c) 2016 Filatova E.N., Anisenkova E.V., Presnyakova N.B., Sycheva T.D., Kulova E.A., Utkin O.V.

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