A protective NOD islet-infiltrating CD8+ T cell clone, I.S. 2.15, has in vitro 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).
Pankewycz
O G
OG
Department of Medicine, University of Virginia, Charlottesville 22908.
Guan
J X
JX
Benedict
J F
JF
D000818:Animals; D001483:Base Sequence; D016827:CD8 Antigens / Q000032:analysis*; D002999:Clone Cells; D016207:Cytokines / Q000235:genetics; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D007376:Interleukin-2 / Q000494:pharmacology; D007515:Islets of Langerhans / Q000473:pathology; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D016688:Mice, Inbred NOD; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000032:analysis; D015375:Receptors, Interleukin-2 / Q000032:analysis; D050378:T-Lymphocytes, Regulatory / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000502:physiology
D016827:CD8 Antigens; D016207:Cytokines; D007376:Interleukin-2; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2; D016212:Transforming Growth Factor beta