The migration of pathogenic T cells to the pancreas, and their subsequent activation and proliferation, are important steps in the pathogenesis of type I diabetes. CD98 is a heterodimeric transmembrane protein that functions in amino acid transport and integrin signaling. Integrin expression and function are important for autoimmune diabetes in the NOD mouse model, and proliferation of T cells in pancreatic draining lymph nodes is a hallmark of disease. Therefore we have begun investigating CD98 as a potential target in type I diabetes. Our preliminary data shows that T cells in which CD98 has been targeted are unable to transfer disease, while transfer of control T cells causes beta cell destruction and overt diabetes. Our overall hypothesis is that CD98 controls migration or proliferation of diabetogenic T cells, and thus is a potential target for disease intervention. The research proposed in this application will Investigate the cellular and biochemical mechanisms by which CD98 deletion protects from type I diabetes, and to study potential side effects of CD98 targeting on normal immune responses.

Public Health Relevance

Blocking the autoimmune attack mediated by lymphocytes in type I diabetes is a high priority, both to prevent the disease, and to stop its recurrence after islet cell transplant. We found that deleting CD98 on T lymphocyte immune cells makes them unable to cause experimental type I diabetes. We are proposing to investigate the mechanism of this protection, and to test what CD98 targeting might do to normal immune responses.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Scientist Development Award - Research & Training (K01)
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Diabetes, Endocrinology and Metabolic Diseases B Subcommittee (DDK)
Program Officer
Hyde, James F
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University of California San Diego
Internal Medicine/Medicine
Schools of Medicine
La Jolla
United States
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Lagarrigue, Frederic; Gertler, Frank B; Ginsberg, Mark H et al. (2017) Cutting Edge: Loss of T Cell RIAM Precludes Conjugate Formation with APC and Prevents Immune-Mediated Diabetes. J Immunol 198:3410-3415
Abplanalp, Wesley T; Conklin, Daniel J; Cantor, Joseph M et al. (2016) Enhanced Integrin ?4?1-Mediated Adhesion Contributes to a Mobilization Defect of Endothelial Progenitor Cells in Diabetes. Diabetes 65:3505-3515
Ablack, Jailal N G; Metz, Patrick J; Chang, John T et al. (2015) Ubiquitylation of CD98 limits cell proliferation and clonal expansion. J Cell Sci 128:4273-8
Cantor, Joseph M; Rose, David M; Slepak, Marina et al. (2015) Fine-tuning Tumor Immunity with Integrin Trans-regulation. Cancer Immunol Res 3:661-7
Hayes, Gregory M; Chinn, Lawrence; Cantor, Joseph M et al. (2015) Antitumor activity of an anti-CD98 antibody. Int J Cancer 137:710-20
Cantor, Joseph M (2014) CD98 is a potential target for ablating B cell clonal expansion and autoantibody in multiple sclerosis. J Neuroimmunol 274:230-3
Cantor, Joseph M; Ginsberg, Mark H (2012) CD98 at the crossroads of adaptive immunity and cancer. J Cell Sci 125:1373-82
Cantor, Joseph; Slepak, Marina; Ege, Nil et al. (2011) Loss of T cell CD98 H chain specifically ablates T cell clonal expansion and protects from autoimmunity. J Immunol 187:851-60