DR-BB rat thymus contains thymocyte populations predisposed to autoreactivity

Area of Science:

• Immunology
• Endocrinology
• Genetics

Background:

• Autoimmune diabetes, specifically insulin-dependent diabetes mellitus (IDDM), can be induced via cell transfer.
• DR-BB rats are prone to IDDM, especially when regulatory T-cells (RT6.1+) are depleted.
• Athymic rats provide a model to study T-cell mediated autoimmunity.

Purpose of the Study:

• To investigate the role of thymocytes in the development of autoimmune diabetes in DR-BB rats.
• To identify the specific T-cell populations responsible for transferring IDDM.
• To pinpoint the developmental stage and location of the defect leading to diabetes in BB rats.

Main Methods:

• Induction of IDDM in athymic WAG rats through transfusion of thymocytes from DR-BB rats.
• Depletion of regulatory T-cells (RT6.1+) in both donor and recipient rats.
• Comparison of thymocyte transfer from normal DR-BB rats, RT6.1-depleted DR-BB rats, and normal YOS rats.
• Assessment of the autoreactive potential of DR-BB rat thymocytes at different ages.

Main Results:

• Adoptive transfer of IDDM was successful using DR-BB thymocytes, but only when recipients lacked RT6.1+ T-cells.
• Thymocytes from both normal and RT6.1-depleted diabetic DR donors effectively transferred autoimmunity.
• Thymocytes from normal YOS rats did not transfer IDDM.
• The autoreactive potential of DR-BB thymocytes increased significantly between 4 and 8-9 weeks of age.

Conclusions:

• The thymus of DR-BB rats contains abnormal cell populations that are predisposed to autoreactivity.
• The developmental defect causing diabetes in BB rats is localized to an aberrant intrathymic selection process.
• Specific T-cell populations within the thymus are critical for the development of autoimmune diabetes.