Email this article PHENOTYPIC AND FUNCTIONAL CHARACTERISTICS OF EARLY THYMIC EMIGRANTS IN PERIPHERAL BLOOD IN NORMAL CONDITIONS AND AUTOIMMUNE DISEASES
- Authors: Abramova T.Y.1, Boeva O.S.1, Angelskaya O.A.2, Borisevich V.I.3, Abbasova V.S.3, Korolev M.А.4, Omelchenko V.O.4, Kurochkina Y.D.4, Rybakova A.D.4, Blinova E.A.1
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Affiliations:
- Research Institute of Fundamental and Clinical Immunology
- City Hospital No. 3
- Novosibirsk State Medical University
- Research Institute of Clinical and Experimental Lymрhology – Branch of the Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences
- Issue: Vol 28, No 3 (2025)
- Pages: 757-764
- Section: SHORT COMMUNICATIONS
- Submitted: 27.02.2025
- Accepted: 25.05.2025
- Published: 18.09.2025
- URL: https://rusimmun.ru/jour/article/view/17101
- DOI: https://doi.org/10.46235/1028-7221-17101-PAF
- ID: 17101
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Abstract
Abstract
Complex mechanisms of thymus functioning affect the structural matrix, contributing to the gradual accumulation of genetic mutations, changes in gene expression and premature immunosenescence. The study of early thymic migrants (RTE) is necessary to identify possible diagnostic biomarkers and potential checkpoints of autoimmune diseases. The object of the study were peripheral blood samples of patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), psoriasis (PS) and healthy donors. The aim of the study was to assess the ratio of recently migrated cells from the thymus and naive T-regulatory cells in the periphery in health and autoimmune pathology. The relative number of recent thymic migrants CD4+CD45RA+CD31+ (RTE) and the number of Foxp3+ T-regulatory cells (Treg) among them were determined by flow cytofluorimetry. The number of proliferating cells was determined by the intracellular Ki-67 content. The analysis showed that the number of RTE was reduced in the group of patients with RA and patients with PsA relative to the donor group (17.3%, 18.6% vs. 23.6%) and did not change significantly in patients with psoriasis. There were no significant differences between donors and patients with AID in the number of proliferating RTE and Tregs. The level of proliferation of T-regulatory cells in patients with psoriatic pathology was comparable to donor values, and in RA there was a tendency to an increase. In patients with RA, the number of proliferating naive Foxp3+ Tregs was significantly higher than the number of proliferating RTE (15.8% vs 3.1%, p<0.05, respectively). A decrease in the relative number of RTE in AID may be associated with the activation of T lymphocytes and an increase in the proportion of central memory T cells. The number of Tregs among RTE and the level of their proliferation in patients with psoriatic pathology, indicate the absence of disturbances in the generation of T-reg in the thymus. The ambiguous results obtained in patients with RA, require additional confirmation on a larger sample of patients.
About the authors
Tatiana Ya. Abramova
Research Institute of Fundamental and Clinical Immunology
Author for correspondence.
Email: tatjana-abramova@mail.ru
ORCID iD: 0000-0002-6947-2212
PhD, MD (Medicine), Leading Researcher, Laboratory of Clinical Immunopathology
Russian Federation, 14 Yadrintsevskaya St, Novosibirsk, 630099Olga S. Boeva
Research Institute of Fundamental and Clinical Immunology
Email: starchenkova97@gmail.com
ORCID iD: 0000-0003-2720-0961
Postgraduate Student, Laboratory of Clinical Immunopathology
Russian Federation, 14 Yadrintsevskaya St, Novosibirsk, 630099Olga A. Angelskaya
City Hospital No. 3
Email: anolga@mail.ru
ORCID iD: 0009-0002-7624-2279
Dermatovenerologist
Russian Federation, NovosibirskVadim I. Borisevich
Novosibirsk State Medical University
Email: borvad2001@mail.ru
ORCID iD: 0009-0001-2731-6887
Student
Russian Federation, NovosibirsVeronika S. Abbasova
Novosibirsk State Medical University
Email: abbasovaveronik@gmail.com
ORCID iD: 0009-0003-6038-4990
Student
Russian Federation, NovosibirskMaksim А. Korolev
Research Institute of Clinical and Experimental Lymрhology – Branch of the Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences
Email: kormax@bk.ru
ORCID iD: 0000-0002-4890-0847
PhD, MD (Medicine), Rheumatologist, Head, Laboratory of Connective Tissue Pathology
Russian Federation, NovosibirskVitaliy O. Omelchenko
Research Institute of Clinical and Experimental Lymрhology – Branch of the Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences
Email: v.o.omelchenko@gmail.com
ORCID iD: 0000-0001-6606-7185
PhD (Medicine), Rheumatologist, Department of Rheumatology, Researcher, Laboratory of Connective Tissue Pathology
Russian Federation, NovosibirskYuliya D. Kurochkina
Research Institute of Clinical and Experimental Lymрhology – Branch of the Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences
Email: juli_k@bk.ru
ORCID iD: 0000-0002-7080-777X
PhD (Medicine), Rheumatologist, Department of Rheumatology, Researcher, Laboratory of Connective Tissue Pathology
Russian Federation, NovosibirskAnna D. Rybakova
Research Institute of Clinical and Experimental Lymрhology – Branch of the Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences
Email: a.rybakova1@g.nsu.ru
Junior Researcher, Laboratory of Pharmacological Modeling dnd Screening of Bioactive Molecules
Russian Federation, NovosibirskElena A. Blinova
Research Institute of Fundamental and Clinical Immunology
Email: blinovaelena-85@yandex.ru
ORCID iD: 0000-0003-3327-3630
PhD (Biology), Senior Researcher, Laboratory of Clinical Immunopathology
Russian Federation, 14 Yadrintsevskaya St, Novosibirsk, 630099References
- Ao Y.Q., Jiang J.H., Gao J., Wang H.K., Ding J.Y. Recent thymic emigrants as the bridge between thymoma and autoimmune diseases. Biochim. Biophys. Acta Rev. Cancer, 2022, Vol. 1877, no. 3, 188730. doi: 10.1016/ j.bbcan.2022.188730.
- Azevedo R.I., Soares M.V., Barata J.T., Tendeiro R., Serra-Caetano A., Victorino R.M., Sousa A.E. IL-7 sustains CD31 expression in human naive CD4+ T cells and preferentially expands the CD31+ subset in a PI3K-dependent manner. Blood, 2009, Vol. 113, no. 13, pp. 2999-3007.
- Houston E.G. Jr., Fink P.J. MHC drives TCR repertoire shaping, but not maturation, in recent thymic emigrants. J. Immunol., 2009, Vol. 183, no. 11, pp. 7244-7249.
- James K.D., Cosway E.J., Lucas B., White A.J., Parnell S.M., Carvalho-Gaspar M., Tumanov A.V., Anderson G., Jenkinson W.E. Endothelial cells act as gatekeepers for LTβR-dependent thymocyte emigration. J. Exp. Med., 2018, Vol. 215, no. 12, pp. 2984-2993.
- James K.D., Cosway E.J., Parnell S.M., White A.J., Jenkinson W.E., Anderson G. Assembling the thymus medulla: Development and function of epithelial cell heterogeneity. Bioessays, 2024, Vol. 46, no. 3, e2300165. doi: 10.1002/bies.202300165.
- Junge S., Kloeckener-Gruissem B., Zufferey R., Keisker A., Salgo B., Fauchere J.C., Scherer F., Shalaby T., Grotzer M., Siler U., Seger R., Güngör T. Correlation between recent thymic emigrants and CD31+ (PECAM-1) CD4+ T cells in normal individuals during aging and in lymphopenic children. Eur. J. Immunol., 2007, Vol. 37, no. 11, pp. 3270-3280.
- Kohler S., Thiel A. Life after the thymus: CD31+ and CD31- human naive CD4+ T-cell subsets. Blood, 2009, Vol. 113, no. 4, pp. 769-774.
- Kolerova A.V., Mikailova D.A., Beimanova M.A., Blinova E.A. Сharacterization of central and effector CD4+ memory cells in psoriasis. Medical Immunology (Russia), 2021, Vol. 23, no. 4, pp. 969-974. doi: 10.15789/1563-0625-COC-2288.
- Legoux F.P., Lim J.B., Cauley A.W., Dikiy S., Ertelt J., Mariani T.J., Sparwasser T., Way S.S., Moon J.J. CD4+ T cell tolerance to tissue-restricted self antigens is mediated by antigen-specific regulatory T cells rather than deletion. Immunity, 2015, Vol. 43, no. 5, pp. 896-908.
- Paiva R.S., Lino A.C., Bergman M.L., Caramalho I., Sousa A.E., Zelenay S., Demengeot J. Recent thymic emigrants are the preferential precursors of regulatory T cells differentiated in the periphery. Proc. Natl. Acad. Sci. USA, 2013, Vol. 110, no. 16, pp. 6494-6499.
- Silva S.L., Albuquerque A.S., Matoso P., Charmeteau-de-Muylder B., Cheynier R., Ligeiro D., Abecasis M., Anjos R., Barata J.T., Victorino R.M., Sousa A.E. IL-7-Induced Proliferation of Human Naive CD4 T-Cells Relies on Continued Thymic Activity. Front. Immunol., 2017, Vol. 8, 20. doi: 10.3389/fimmu.2017.00020. PMC5243809.
- Takahashi T., Tagami T., Yamazaki S., Uede T., Shimizu J., Sakaguchi N., Mak T.W., Sakaguchi S. Immunologic self-tolerance maintained by CD25(+)CD4(+) regulatory T cells constitutively expressing cytotoxic T lymphocyte-associated antigen 4. J. Exp. Med., 2000, Vol. 192, no. 2, pp. 303-310.
- Taves M.D., Ashwell J.D. Glucocorticoids in T cell development, differentiation and function. Nat. Rev. Immunol., 2021, Vol. 21, no. 4, pp. 233-243.
- Thiault N., Darrigues J., Adoue V., Gros M., Binet B., Perals C., Leobon B., Fazilleau N., Joffre O.P., Robey E.A., van Meerwijk J.P., Romagnoli P. Peripheral regulatory T lymphocytes recirculating to the thymus suppress the development of their precursors. Nat. Immunol., 2015, Vol. 16, no. 6, pp. 628-634.
- Wildin R.S., Ramsdell F., Peake J., Faravelli F., Casanova J.L., Buist N., Levy-Lahad E., Mazzella M., Goulet O., Perroni L., Bricarelli F.D., Byrne G., McEuen M., Proll S., Appleby M., Brunkow M.E. X-linked neonatal diabetes mellitus, enteropathy and endocrinopathy syndrome is the human equivalent of mouse scurfy. Nat. Genet., 2001, Vol. 27, no. 1, pp. 18-20.
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