Study into the influence of selected drugs and immunomodulators on the activity of regulatory T lymphocytes (Treg)

Regulatory T cells (Treg) are responsible for suppressing the immune system response. They play a key role in the proper functioning of the immune system. Their abnormal function is seen in many diseases, such as autoimmune diseases, allergies, as well as in the process of transplant rejection. The search for compounds that induce these lymphocytes or enhance their activity is of great importance in the development of new methods of treating many diseases. The proposed studies will determine the effect of various immunomodulators and drugs on the activity of T regulatory lymphocytes. Lymphocytes will be isolated from the peripheral blood of healthy donors (coats), and then Treg lymphocytes (lymphocytes suppressing the immune response) will be induced in the culture. In the preliminary studies to date, we have observed that butyric acid and inosine pranobex increase the number of Treg lymphocytes (CD4 + CD25h19hFoxp3 + phenotype) in culture. In addition, therapeutics such as rapamycin, glatiramer acetate, atorvastatin, vitamin D3 and prednisolone will be investigated. In the next stage, it will be shown whether the tested compounds affect the functionality of Treg lymphocytes. For this purpose, a functional test will be used to determine how lymphocyte function changes depending on the drug used. This test will determine whether these therapeutics could potentially be used to stimulate the activity of pathological regulatory T lymphocytes in patients with their deficiency. It will consist in testing the ability of Treg lymphocytes, after their incubation with the investigational drugs, to inhibit the proliferation of effector lymphocytes. In the last stage of the experiment, it will be examined whether the tested drugs can be used for therapeutic purposes in patients suffering from myasthenia gravis - a representative autoimmune disease. Treg lymphocytes in patients from this group have impaired function, which is one of the reasons for the onset of the disease. Lymphocytes from the peripheral blood of patients with newly diagnosed myasthenia gravis will be isolated, and then Treg lymphocytes will be induced in in vitro culture. It will then be determined whether the immunomodulators restore the normal activity of the pathological lymphocytes in the functional test described above using peptides derived from acetylcholine receptors (AChR) as stimulators of specific reactions. The proposed research may be important in the treatment of, inter alia, autoimmune diseases, allergies, graft versus host disease, or in inducing transplant tolerance.