Immunoregulatory Effect of Anti-thymocyte Globulin Monotherapy on Peripheral Lymphoid Tissues of Non-obese Diabetic Mice

• Published in: Transplantation proceedings 2011-11, Vol.43 (9), p.3277-3280
• Main Authors: Vargova, L, Zacharovova, K, Dovolilova, E, Vojtova, L, Saudek, F
• Format: Article
• Language: English
• Subjects: Animals; Antilymphocyte Serum - therapeutic use; Autoimmunity; Biological and medical sciences; Blood Glucose - metabolism; Diabetes Mellitus, Experimental - immunology; Diabetes Mellitus, Experimental - therapy; Diabetes Mellitus, Type 1 - immunology; Diabetes Mellitus, Type 1 - therapy; Female; Flow Cytometry - methods; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Glucose Tolerance Test; Hyperglycemia - immunology; Immune System; Lymphoid Tissue - metabolism; Medical sciences; Mice; Mice, Inbred NOD; Surgery; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Time Factors; Tissue, organ and graft immunology; Treatment Outcome
• ISSN: 0041-1345; 1873-2623
• DOI: 10.1016/j.transproceed.2011.09.057

Abstract Objective Experimental and clinical studies have shown that autoimmunity-causing diabetes may be abrogated by immune intervention. Several anti–T-lymphocyte antibodies focus on distinct T-cell targets. We tested the effect of murine anti-thymocyte globulin (ATG; Genzyme, Framingham, MA) in peripheral lymphoid organs of non-obese diabetic (NOD) mice after the onset of hyperglycemia. Methods Diabetic NOD mice were treated with two doses of ATG (1 mg totally) or maintained without treatment as controls. Blood glucose levels were monitored twice a week. The mice were terminated at day 0, 7, 14, or 28 after the initiation of the study. Subpopulations of T-lymphocytes and FoxP3+ (forkhead box P3 positive) regulatory T-cells were analyzed among elements isolated from the spleen and pancreatic lymph nodes. Results Mice with blood glucose levels greater than 13 mmol/L were included in the study. Diabetes remission occurred in 16% (3/19) of mice treated with ATG. Only one case of remission was observed in the control group (6%; 1/16). ATG therapy a significantly decreased the CD8+/CD4+ T-lymphocyte ratio. Among splenocytes, a significant difference was detected only on day 7 (0.069 versus 0.198 T-lymphocyte ratio); in lymph nodes, a decrease was observed on day 28 (0.21 versus 0.51 T-lymphocytes ratio). The regulatory T-cells population increased after ATG administration compared with the control group at day 7 (16.2% versus 10.8% in CD4+ splenocytes; 20.7% versus 10.3% in CD4+ lymph node cells). However, the increased FoxP3+ cell population was not durable. Conclusions ATG treatment of diabetic NOD mice showed an immunoregulatory effect in peripheral lymphoid tissue with a significantly deceased CD8+/CD4+ ratio, which, however, did not normalize the metabolic parameters in a short period after the onset of overt diabetes.