EXPERIMENTAL MODEL OF SJOGREN'S SYNDROME ACCOMPANIED BY T LYMPHOCYTOPENIA



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Abstract

Abstract

Sjogren's syndrome (SS) is a systemic autoimmune disease characterized by immune-mediated damage to the salivary and lacrimal glands. SS severity and mortality correlate with peripheral CD3 T lymphopenia, which accompanies Sjogren's syndrome in 5-35% of cases. The mechanism underlying the development of lymphopenia in SS remains unclear. Experimental model is an important tool for studying disease mechanisms. Sjogren's syndrome model replicates salivary gland damage typical for human primary SS, but does not reproduce lymphopenia symptoms. Sjogren's syndrome was induced in Wistar rats via intradermal immunization with 10-35 kDa proteins emulsified in CFA, followed by booster injections in CFA and in IFA on day 14 and 28, respectively. The proteins were isolated from the homogenate of mouse salivary glands by size-exclusion chromatography on SepFast SEC 3-70 sorbent. The number of CD3, CD3CD4 and CD3CD8 lymphocytes was determined by flow cytometry. Histological analysis of submandibular salivary gland sections was performed 12 weeks after the initial immunization. The analysis revealed that 33% of rats exhibited damage to the epithelium of granular ducts and multiple foci of ductal epithelium hyperplasia. We suggest a transient nature of the induced autoimmune reaction against salivary gland antigen, as no lymphocytic infiltration was detected in histological analysis. In addition, chronic CD4 and CD8 T lymphopenia was detected in 50% of rats immunized with salivary gland proteins. Thus, we have developed an experimental model of Sjogren's syndrome, which reproduced not only salivary gland damage, but also chronic CD4 and CD8 lymphopenia. This model may serve as a valuable tool for elucidating the mechanisms underlying lymphopenia in Sjogren’s syndrome.

About the authors

Liubov V Beduleva

Udmurt State University, Laboratory of Molecular and Cell Immunology, Izhevsk;
Udmurt Federal Research Center UB RAS, Laboratory of Biocompatible Materials, Izhevsk

Email: blv76@mail.ru

PhD, MD (Biology), Professor, Chief Research Associate, Laboratory of Molecular and Cell Immunology, Udmurt State University;

Leading Research Associate, Laboratory of Biocompatible Materials, Udmurt Federal Research Center, Ural Branch, Russian Academy of Sciences

Russian Federation, 426034, Izhevsk, Universitetskaya St, 1.; 426067, Izhevsk, Baramzinoy St, 34.

Kseniya V Fomina

Udmurt State University, Laboratory of Molecular and Cell Immunology, Izhevsk;
Udmurt Federal Research Center UB RAS, Laboratory of Biocompatible Materials, Izhevsk

Email: fomiksa@yandex.ru

PhD (Biology), Senior Research Associate, Laboratory of Molecular and Cell Immunology, Udmurt State University;

Senior Research Associate, Laboratory of Biocompatible Materials, Udmurt Federal Research Center, Ural Branch, Russian Academy of Sciences.

Russian Federation, 426034, Izhevsk, Universitetskaya St, 1.; 426067, Izhevsk, Baramzinoy St, 34.

Daria I Menshikova

Udmurt State University, Laboratory of Molecular and Cell Immunology, Izhevsk

Email: daaurum947@gmail.com

Research Engineer, Laboratory of Molecular and Cell Immunology, Udmurt State University.

Russian Federation, 426034, Izhevsk, Universitetskaya St, 1.

Oksana S Terentievа

Udmurt State University, Laboratory of Molecular and Cell Immunology, Izhevsk

Email: terent-oksana@yandex.ru

Junior Researcher Associate, Laboratory of Molecular and Cell Immunology, Udmurt State University

Russian Federation, 426034, Izhevsk, Universitetskaya St, 1.

Danil P Yushkov

Udmurt State University, Laboratory of Molecular and Cell Immunology, Izhevsk

Author for correspondence.
Email: far-manag@yandex.ru

Research Engineer, Laboratory of Molecular and Cell Immunology, Udmurt State University

Russian Federation, 426034, Izhevsk, Universitetskaya St, 1.

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Copyright (c) Beduleva L.V., Fomina K.V., Menshikova D.I., Terentievа O.S., Yushkov D.P.

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