A novel function of islet-derived CD8+T cells in initiating and developing autoimmune insulin-dependent diabetes mellitus in non-obese diabetic (NOD) mice.
Accumulated studies revealed that CD4+T cells were initially required for diabetes in NOD mice, whereas interaction of CD4+T/CD8+T cells is not fully understood. To address this question, we established islet-derived CD4+T cells and CD8+T cells from NOD mice. One NOD neonate that received CD4+T cells developed diabetes and insulitis with CD8+T cells. Administration of cyclophosphamide to non-diabetic recipients accelerated the development of diabetes, while none of the mice with anti-CD8 antibody did so. Similarly, it was observed that neonates that received islet-derived CD8+T cells developed diabetes and obvious insulitis mainly with CD4+T cells. Administration of anti-CD4 antibody with transfer of CD8+T cells inhibited insulitis. These results imply that CD8+T cells function as an initial element to recruit CD4+T cells to islets as well as a final effector.
Amano
K
K
Second Department of Internal Medicine, Kobe University School of Medicine, Japan.
Yokono
K
K
Hasegawa
Y
Y
Taki
T
T
Tominaga
Y
Y
Yoneda
R
R
Nagata
M
M
Kasuga
M
M
D000818:Animals; D000911:Antibodies, Monoclonal; D015704:CD4 Antigens / Q000276:immunology / Q000502:physiology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D002469:Cell Separation; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D005434:Flow Cytometry; D006825:Hybridomas; D007515:Islets of Langerhans / Q000276:immunology* / Q000473:pathology; D008213:Lymphocyte Activation; D051379:Mice; D016688:Mice, Inbred NOD; D010182:Pancreatic Diseases / Q000276:immunology / Q000473:pathology
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens