Critical roles of CD30/CD30L interactions in murine autoimmune diabetes.
CD30/CD30L is a member of tumour necrosis factor (TNF) receptor/TNF superfamily and has been implicated in immune-regulation. A genetic study has also suggested a possible implication of CD30 in spontaneous autoimmune diabetes in NOD mice. In this study, we investigated the involvement of CD30/CD30L in the development of diabetes in NOD mice. Flow cytometric analysis showed that CD30 and CD30L were highly expressed on CD4+ or CD8+ T cells in the spleen and pancreatic lymph node of younger NOD mice. In addition, islet-specific CD4+ or CD8+ T cell lines expressed CD30 and CD30L. Administration of a neutralizing anti-CD30L monoclonal antibody (mAb) from 2 to 10 week of age completely suppressed the development of spontaneous diabetes in NOD mice. In addition, the treatment with anti-CD30L mAb also inhibited the development of diabetes induced by adoptive transfer of spleen cells from diabetic NOD mice or islet-specific CD4+ or CD8+ T cell lines into NOD-SCID mice. Furthermore, anti-CD30L mAb inhibited T cell proliferation in response to islet antigens. These results suggested that CD30/CD30L interaction plays important roles in both induction and effector phases of autoimmune diabetes in NOD mice.
Chakrabarty
S
S
Division of Internal and Geriatric Medicine, Department of Development and Ageing, Kobe University Graduate School of Medicine, Kobe, Japan.
Nagata
M
M
Yasuda
H
H
Wen
L
L
Nakayama
M
M
Chowdhury
S A
SA
Yamada
K
K
Jin
Z
Z
Kotani
R
R
Moriyama
H
H
Shimozato
O
O
Yagita
H
H
Yokono
K
K
D019264:Adoptive Transfer / Q000379:methods; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001327:Autoimmune Diseases / Q000276:immunology*; D053285:CD30 Ligand; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003921:Diabetes Mellitus, Experimental / Q000276:immunology*; D005260:Female; D007515:Islets of Langerhans / Q000276:immunology; D017730:Ki-1 Antigen / Q000276:immunology*; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D013601:T-Lymphocytes / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D000911:Antibodies, Monoclonal; D053285:CD30 Ligand; D017730:Ki-1 Antigen; D008562:Membrane Glycoproteins; C505775:Tnfsf8 protein, mouse