Disequilibrium in the CD8 + CD28 + /CD8 + CD28 − T Lymphocyte Balance Is Related to Prognosis in Rats with Trinitrobenzenesulfonic Acid-Induced Colitis

Abstract

Purpose

The CD8⁺CD28⁺/CD8⁺CD28⁻ T lymphocyte balance is vital for human ulcerative colitis (UC) but has not been defined in experimental colitis. This investigation will try to identify the changes that occur in the CD8⁺CD28⁺/CD8⁺CD28⁻ T lymphocyte balance during the progression of trinitrobenzenesulfonic acid (TNBS)-induced colitis in rats.

Methods

The frequencies of blood CD8⁺CD28⁺ and CD8⁺CD28⁻ T lymphocytes were detected in the rats belonging to the normal, model, and treated groups on five days using flow cytometry. The treated rats were administered with mesalazine and were euthanized after a 14-day treatment, as were the normal and model rats. The sensitivity and specificity of the CD8⁺CD28⁺/CD8⁺CD28⁻ T lymphocyte balance in diagnosing early colitis were analyzed by receiver operating characteristics (ROC) curves. The frequencies of CD8⁺CD28⁺ and CD8⁺CD28⁻ T lymphocytes in the colon tissue were tested via immunofluorescence. ELISA was used to measure the levels of the cytokines. Immunohistochemistry and Western blotting were used to detect the colonic expression of JAK3, STAT6, NFATc2, and GATA3.

Results

We found that the ratio of CD8⁺CD28⁺/CD8⁺CD28⁻ T lymphocytes decreased, as did the level of interleukin-7, but not IL-12p40, IL-13, or IL-15, in the blood; however, the ratio increased along with JAK3, STAT6, NFATc2, and GATA3 in the colon of the rats with colitis. The changes were effectively reversed through the administration of mesalazine for 13 days. Surprisingly, the balance in the blood could sensitively distinguish rats with early colitis from normal rats.

Conclusion

These data show that increase in CD8⁺CD28⁺ T cells in blood and decrease in CD8⁺CD28⁻ T cells in colon are associated with experimental colitis.

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