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Diabetes Publish Ahead of Print published online ahead of print June 27, 2007
DOI: 10.2337/db07-0502

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Original Research

Bone Marrow is a Preferential Homing site for Autoreactive T cells in type 1 diabetes

Ruobing Li, Nicolas Perez, Subha Karumuthil-Melethil, and Chenthamarakshan Vasu

Department of Surgery, University of Illinois at Chicago, Chicago, IL-60612, USA

Correspondence: chenta{at}uic.edu

Key Words: Type 1 diabetes • Autoimmunity • T cells • Bone marrow.

Objective:Pancreatic microenvironment is considered as the primary location of autoreactive T cells in type 1 diabetes. Diabetogenic T cells have also been detected in the spleen of NOD mice. However, it is not known whether the BM also contains T cells specific for self-antigen in hosts with autoimmunity. In this study, we investigated whether autoreactive diabetogenic T cells are present in the BM of NOD mice.

Research Design and Methods:BM and spleen T cells of female NOD mice were purified and tested for their cytokine secretion and proliferation in response to stimulation with immuno-dominant peptides of pancreatic ß cells. The diabetogenic nature and homing properties of purified BM T cells were compared with that of spleen T cells in NOD-Scid and wild-type mice.

Results:The BM T cells from both hyperglycemic and young euglycemic mice demonstrated profoundly higher proliferation and cytokine production in response to stimulation with ß-cell antigens as compared to T cells from spleen. The BM T cells showed rapid expansion and aggressive infiltration into pancreatic islets in NOD-Scid mice and induced hyperglycemia earlier than that observed with splenic T cells. Adoptive transfer of BM T cells resulted in their trafficking predominantly into BM and pancreatic LNs.

Conclusion:Our study shows that a large number of diabetogenic T cells are present in the BM of female NOD mice and these autoreactive T cells can be detected much before the clinical onset of the disease.



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