Rheumatoid regulatory factor in the blood of rats immunized with autologous lymphocytes, activated in vitro by heterologous lymphocytes

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Abstract

The approaches to prevention of acute and chronic transplant rejection are among the important challenges in clinical transplantology and regenerative medicine. For more than a century, induction of tolerance to natural and artificial transplant antigens has been a desired goal. Recently, anti-lymphocytic antibodies to activated lymphocytes, called regulatory rheumatoid factor (regRF), are shown to be involved in control of autoreactive lymphocytes under normal conditions, thus maintaining natural immune tolerance. A relatively rapid increase in the level of regRF in the blood (3-5 days) after immunization is observed during autotransplantation. Its early rise is also associated with non-reactivity of animals to experimentally induced autoimmune disorders. The aim of our study was to search an opportunity of regRF production in rats by injecting autologous lymphocytes activated in vitro by a heterologous antigen (murine lymphocytes). To achieve this result, a group of rats was immunized intravenously with a mixed culture of autologous and heterologous (murine) lymphocytes (MLC), after 5 days of co-incubation. Another group was immunized with murine lymphocytes only. RegRF in the blood was determined by days 3, 5, 7, 14, 21, 28 and 35 after immunization. It was hypothesized that the intravenous injection of autologous MLC-activated rat lymphocytes and mouse lymphocytes to the rats would cause an early regRF response to autologous lymphocytes, and a later response to heterologous mouse lymphocytes. On average, the regRF titer in rats following immunization with murine lymphocytes did not show significant changes. However, a significant increase in the standard deviation was seen only on day 7, thus indicating to a pronounced individual response of rats to the injection of heterologous murine lymphocytes. Immunization of animals with MLC-activated cells caused a two-phase increase of regRF in blood observed on days 5 and 21. An increase in regRF on day 5 after MLC immunization suggests a response to autologous lymphocytes activated by a heterologous antigen. The obtained results open up a prospect for further research aimed at developing novel techniques for inducing acquired tolerance.

About the authors

Anastasia V. Kryazhevskikh

Udmurt Federal Research Center, Ural Branch, Russian Academy of Sciences; Udmurt State University

Author for correspondence.
Email: krav526@gmail.com

Research Engineer, Laboratory of Biocompatible Materials, Postgraduate Student, Department of Immunology and Cell Biology

Russian Federation, Izhevsk, Udmurt Republic; Izhevsk, Udmurt Republic

N. N. Abisheva

Udmurt Federal Research Center, Ural Branch, Russian Academy of Sciences; Udmurt State University

Email: krav526@gmail.com

PhD (Biology), Senior Researcher, Laboratory of Biocompatible Materials, Senior Researcher, Laboratory of Molecular and Cellular Immunology, Associate Professor, Department of Immunology and Cell Biology

Russian Federation, Izhevsk, Udmurt Republic; Izhevsk, Udmurt Republic

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2. Figure 1. The level of regRF in the blood of rats after the introduction of heterologous (mouse) lymphocytes (group 1), after the introduction of autologous lymphocytes activated in vitro by heterologous (mouse) lymphocytes (group 2) Note. The figure shows the average values ± SD. RegRF was assessed by the agglutination method of tanized erythrocytes loaded with homologous IgG.

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3. Figure 2. The level of regRF in rats with auto- (n = 10), allo- (n = 10), and xenotransplantation (n = 8) of skin during 28 days of the experiment Note. As for Figure 1.

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