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Science 19 February 1993:
Vol. 259. no. 5098, pp. 1165 - 1169
DOI: 10.1126/science.8267690
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Articles

Science, Vol 259, Issue 5098, 1165-1169
Copyright © 1993 by American Association for the Advancement of Science

articles

Progression to diabetes in nonobese diabetic (NOD) mice with transgenic T cell receptors

MA Lipes, A Rosenzweig, KN Tan, G Tanigawa, D Ladd, JG Seidman, and GS Eisenbarth

Joslin Diabetes Center, Harvard Medical School, Brigham and Women's Hospital, Boston, MA 02115.

The T cell receptor (TCR) requirements in the pathogenesis of insulin-dependent diabetes were examined with transgenic NOD mice bearing nondisease-related TCR alpha and beta chains. In both TCR beta and TCR alpha beta transgenic NOD mice the beta chain transgene was expressed by > 98% of peripheral T cells. The alpha chain transgene was also highly expressed. Insulitis developed in both sets of transgenic animals with most of the lymphocytes in the lesion expressing the transgenic beta chain and with depletion of the endogenous TCR V beta genes. Nonetheless, NOD animals transgenic for TCR beta and TCR alpha beta developed diabetes similar to controls. Thus, skewing the TCR repertoire did not diminish autoimmune susceptibility in NOD mice.


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Response.
M. A. Lipes, A. Rosenzweig, K.-N. Tan, G. Tanigawa, J. G. Seidman, and G. S. Eisenbarth (1993)
Science 262, 1584
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