The significance of immunoregulatory receptor TIGIT expression in thymus and peripheral blood mononuclear cells in an “anger” rat model

doi:10.3969/j.issn.2095-4344.2765

Abstract

Abstract:

BACKGROUND: Previous studies have shown that stress response can cause immune dysfunction in the body. T cell immunoglobulin and ITIM domain (TIGIT) is an immunoregulatory receptor that can inhibit T cell activity, promote T cell apoptosis and promote T cell subgroup distribution imbalance. Whether the immune response mechanism of stress response is related to the expression and function of TIGIT is still unclear.

OJECTIVE: To investigate the expression of immunomodulatory receptor TIGIT in thymus cells and peripheral blood mononuclear cells in an anger rat model and its significance to immune function.

METHODS: Forty-eight Wistar male rats were randomly divided into normal group, 7-, 14- and 21-day model groups, with 12 rats in each group. In addition to the blank group, social isolation method with plantar electric shock method was used to establish rat anger models in the other groups. The behavioral changes of rats were observed by open-field test and aggressive behavior test, and the changes in body mass and thymus index before and after the test were recorded. The positive expression of TIGIT in thymus and peripheral blood mononuclear cells of rats in each group was observed by immunohistochemistry, and the expression levels of CD4⁺ and CD8⁺ T cells in the peripheral blood were measured by flow cytometry. The correlation between TIGIT expression in thymus and peripheral blood mononuclear cells and the CD4⁺/CD8⁺ ratio of T cell subsets in the peripheral blood was analyzed. An ethical approval for the study was obtained from the Animal Ethics Committee of Jiangxi University of Traditional Chinese Medicine.

RESULTS AND CONCLUSION: In the 14- and 21-day model groups, the scores of horizontal and vertical activities in the open-field test of rats were higher than the control group (P < 0.05 or P < 0.01). In the 7-, 14- and 21-day model groups, the attack hiding time of the attack behavior test was significantly shortened (P < 0.01), the number of attacks and the cumulative attack time were significantly increased (P < 0.01), and the body mass and thymus index were significantly decreased compared with the control group (P < 0.05 or P < 0.01). In the 7- and 14-day model groups, the expression level of TIGIT in thymus and peripheral blood mononuclear cells was significantly higher than the control group (P < 0.01), while the CD4⁺/CD8⁺ ratio level of the peripheral blood T cell subsets was significantly lower than the control group (P < 0.05 or P < 0.01). The CD4⁺/CD8⁺ ratio of T cell subsets in the peripheral blood of random samples of rats was negatively correlated with the expression level of TIGIT in T cells of thymus (r²=0.627 0, P < 0.000 1) and in mononuclear cells (r²=0.624 4, P < 0.000 1). These results indicate that the model rats in the stress-induced anger state have obvious changes in animal behavior, present with thymus atrophy and abnormalities in peripheral blood T lymphocyte subsets CD4⁺/CD8⁺ ratio and immune function. This phenomenon may be related to the thymus and peripheral blood mononuclear cells TIGIT expression level, but the specific mechanism needs to be elucidated further.

Key words: TIGIT, stress, T lymphocyte, thymus, “Anger” model, animal model, immunoregulatory receptor

CLC Number:

Chen Junxian, Li Weiting, Yang Junping, Wang Ying, Jin Guilin.

The significance of immunoregulatory receptor TIGIT expression in thymus and peripheral blood mononuclear cells in an “anger” rat model [J]. Chinese Journal of Tissue Engineering Research, 2020, 24(26): 4183-4189.

Figures/Tables 8

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