A PROTECTIVE NOD ISLET-INFILTRATING CD8+ T-CELL CLONE, IS 2.15, HAS INVITRO IMMUNOSUPPRESSIVE PROPERTIES

Type 1, insulin-dependent diabetes mellitus (IDDM) appears to result from a T cell-dependent destruction of insulin-producing pancreatic beta-cells. In non-obese diabetic (NOD) mice and in other rodent models of human IDDM, final expression of disease may be controlled by protective, as well as, destructive T cell influences. Previously, a CD8+ T cell clone, I.S. 2.15, was isolated directly from islets of disease-resistant male NOD mice. Upon transfer to young NOD recipients, the non-cytolytic I.S. 21.5 T cell clone, confers in vivo protection from two forms of accelerated IDDM. The present study demonstrates that I.S. 2.15 T cells induce in vitro immunosuppression. The suppressive effects of I.S. 2.15 T cells are mediated through soluble factor(s) and are independent of T cell activation, cell contact, antigen specificity or the major histocompatibility complex (MHC). By polymerase chain reaction (PCR), I.S. 2.15 T cells contain mRNA species encoding for the potentially immunosuppressive cytokines, interleukin-10 (IL-10) and transforming growth factor-beta (TGF-beta). The T cell suppressive effects engendered by I.S. 2.15 T cells closely mimic those observed with TGF-beta. Moreover, I.S. 2.15-induced immunosuppression correlates with intracellular levels of TGF-beta mRNA. These results establish that immunoregulatory T cells are present within islets in IDDM-resistant NOD mice and may impact on final disease expression through the production of soluble mediator(s).