Effect of peptides of trophoblastic Β1 glycoprotein on peripheral and local T-regulatory lymphocytes level in Wistar rats with allogeneous bone marrow cell transplantation

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Abstract

Objective. The range of peptide drugs is expanding, but no drug with immunosuppressive activity has yet been found. Considering the fact that the trophoblastic β1-glycoprotein (PSG) is a fetoplacental protein with immunosuppressive activity, short peptide fragments of this protein were studied in the formation of an immune response in a situation of allogeneic cell transplantation. To study the effect of PSG peptides (YECE, YQCE, YVCS, and YACS) on the levels of peripheral and local T-regulatory cells (Treg) during the formation of an immune response to the introduction of allogeneic bone marrow cells (BM) in a dynamic experiment on Wistar rats.

Materials and methods. We used an original host-versus-graft model in male Wistar rats without preconditioning of recipients. Animals were injected with PSG peptide fragment composition against a background of allogeneic intraperitoneal transplantation of BM cells in a dynamic experiment, in which the following parameters were evaluated: the level of peripheral "true" Tregs (CD4+CD25+FOXP3+), CD4+CD25-FOXP3+ cells, and FOXP3 expression in mesenteric lymph nodes. Material was collected on days 3 and 21 of the experiment.

Results. PSG peptide administration against a background of allogeneic BM cells was found to reduce the absolute and relative amount of Treg in the peripheral blood of rats on days 3 and 21 of the experiment. PSG peptides against the background of the introduction of allogeneic BM cells reduced the absolute and relative amounts of CD4+CD25-FOXP3+ cells on the day 3 of the experiment. The introduction of PSG peptides against the background of the introduction of BM cells resulted in a relative decrease in FOXP3 expression in the T zone of mesenteric lymph nodes on the day 21 of the experiment.

Conclusions. Thus, the PSG peptides did not have the expected effect on the level of peripheral and local Treg cells; moreover, the presence of the peptides led to a decrease in the number of these cells.

About the authors

S. А. Zamorina

Perm State National Research University; Institute of Ecology and Genetics of Microorganisms, Ural Branch of RAS

Author for correspondence.
Email: zamorina.sa@gmail.com
ORCID iD: 0000-0002-6474-1487

Doctor of Biological Sciences, Leading Researcher, of the Laboratory of Cellular Immunology and Biotechnology, Professor of the Department of Microbiology and Immunology

Russian Federation, Perm; Perm

М. S. Bochkova

Perm State National Research University; Institute of Ecology and Genetics of Microorganisms, Ural Branch of RAS

Email: zamorina.sa@gmail.com
ORCID iD: 0000-0001-5784-6224

Candidate of Biological Sciences, Researcher of the Laboratory of Cellular Immunology and Biotechnology, Senior Lecturer of the Department of Microbiology and Immunology

Russian Federation, Perm; Perm

V. P. Timganova

Perm State National Research University; Institute of Ecology and Genetics of Microorganisms, Ural Branch of RAS

Email: zamorina.sa@gmail.com
ORCID iD: 0000-0003-4581-1969

Candidate of Biological Sciences, Researcher of the Laboratory of Cellular Immunology and Biotechnology

Russian Federation, Perm

V. V. Vlasova

Пермский государственный национальный исследовательский университет; Институт экологии и генетики микроорганизмов Уральского отделения Российской академии наук – филиал Пермского федерального исследовательского центра Уральского отделения Российской академии наук

Email: zamorina.sa@gmail.com
ORCID iD: 0000-0002-1656-7277

junior researcher, Laboratory of Molecular Immunology, engineer of the Department of Microbiology and Immunology

Russian Federation, Perm; Perm

А. V. Lyubimov

“Imbiocom” LLC

Email: zamorina.sa@gmail.com
ORCID iD: 0009-0002-8732-4210

MD, PhD, Professor, consultant

Russian Federation, Perm

N. P. Loginova

E.A. Vagner Perm State Medical University

Email: zamorina.sa@gmail.com
ORCID iD: 0000-0001-8597-2682

MD, PhD, Associate Professor, Head of the Department of Histology, Embryology and Cytology

Russian Federation, Perm

Yu. A. Charushina

E.A. Vagner Perm State Medical University

Email: zamorina.sa@gmail.com
ORCID iD: 0000-0002-2193-7463

Lecturer, Department of Histology, Embryology and Cytology

Russian Federation, Perm

N. V. Chemurzieva

E.A. Vagner Perm State Medical University

Email: zamorina.sa@gmail.com
ORCID iD: 0009-0006-0228-0896

Candidate of Biological Sciences, Head of the Department of Educational, Methodological and Scientific Support

Russian Federation, Perm

М. B. Rayev

Perm State National Research University; Institute of Ecology and Genetics of Microorganisms, Ural Branch of RAS

Email: zamorina.sa@gmail.com
ORCID iD: 0000-0001-6882-4928

Doctor of Biological Sciences, Head of the Laboratory of Cellular Immunology and Nanobiotechnology, Professor of the Department of Microbiology and Immunology

Russian Federation, Perm; Perm

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2. Fig. 1. Scheme of an in vivo experiment to study the effect of TBG peptides on the level of local and peripheral Tregs

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3. Fig. 2. Absolute (a) and relative (b) number of Tregs (CD4+CD25+FOXP3+) in the peripheral blood of rats with BM allotransplantation and administration of TBH peptides: data are presented as the mean and standard error of the mean; N = 4; * – P < 0.05; ** – P < 0.01; *** – P < 0.001 (two-way ANOVA, post-hoc Tukey test for multiple comparisons)

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4. Fig. 3. Absolute (a) and relative (b) number of CD4+CD25–FOXP3+ cells in the peripheral blood of rats with BM allotransplantation and administration of TBH peptides: data are presented as the mean and standard error of the mean; N = 4; * – P < 0.05; ** – P < 0.01; *** – P < 0.001 (two-way ANOVA, post-hoc Tukey test for multiple comparisons)

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5. Fig. 4. Effect of TBG peptides on the level of FOXP3 expression in the cells of the cortex of mesenteric lymph nodes using the example of individual sections (magnitude X400)

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