T-Lymphocyte Requirement for Diabetes in RT6-Depleted Diabetes-Resistant BB rats

Diabetes-prone (DP) BB rats develop spontaneous autoimmune insulin-dependent diabetes mellitus (IDDM). The cell populations involved in the expression of diabetes are not precisely known but probably include natural killer (NK) cells, macrophages, and T lymphocytes. Because the DP rat has few lymphocytes of the CD5⁺/CD⁺ phenotype, cytotoxic T lymphocytes (T_c) are not believed to be important in the process. Diabetes-resistant (DR) BB rats that are depleted of RT6⁺ T lymphocytes also become diabetic and provide an additional model of IDDM. We report that diabetes in DR rats depleted of RT6⁺ T lymphocytes is prevented by the concomitant depletion of either the CD5⁺ or the CD8⁺ population. In contrast, coadministration of anti-asialoganglioside_M1 (α-ASG_M1), an antiserum that principally recognizes NK cells, failed to prevent hyperglycemia in RT6-depleted rats. We propose that the initiation of diabetes in both DP and RT6-depleted DR rats is T-lymphocyte dependent. However, the final common pathway leading to autoimmune β-cell destruction in IDDM may be different in these models. The RT6-depleted DR rat requires a cell that is sensitive to anti-CD8 (possibly a T_c), whereas the DP rat requires an anti-ASG_M1–sensitive cell.