Diabetes Prone BB Rats are Severely Deficient in Natural Killer T Cells

Abstract

Diabetes prone (DP) BB rats develop spontaneous autoimmune hyperglycemia. Coisogenic diabetes resistant (DR) BB rats develop diabetes in response to immunological and environmental perturbants, but not spontaneously. Both are used to model human insulin-dependent diabetes mellitus (IDDM). Deficiencies in natural killer (NK) T cells have been implicated in the expression of human IDDM, but little is known of their phenotype or function in the rat. We now report that the phenotype of NK T cells in the rat is αβTcR ⁺CD8⁺CD4^-, comparable to the NK T cell phenotype reported for humans, which is αβTcR⁺CD4 Vα24-JαQ, and either CD8 or CD8αα⁺. We also report that DP- but not DR-BB rats are severely deficient in splenic and intrahepatic NKR-P1⁺ αβTcR+ (NK T) cells. Because RT6⁺ T cells are deficient in DP-BB rats, and because depletion of cells expressing RT6 induces IDDM in DR-BB rats, we studied NK T cells for expression of this antigen. We observed that the majority of rat NK T cells express RT6. In addition, injection of cytotoxic anti-RT6.1 monoclonal antibody depleted splenic and intrahepatic RT6⁺ NK T cells, T cells, and NK cells, but left intact the RT6^- subset of each population. These results suggest that deficiencies in NK T cells may play a role in the susceptibility of DP- and DR-BB rats, respectively, to spontaneous and induced autoimmune IDDM.

Key Words:

• NK T cell
• BB rat
• Autoimmunity
• Diabetes
• Intrahepatic lymphocytes