High density insulin receptor-positive T lymphocytes from nonobese diabetic mice transfer insulitis and diabetes.
In the nonobese diabetic mouse, insulin-dependent diabetes is an autoimmune disease characterized by T cell-mediated invasion and destruction of pancreatic islet beta cells. The importance of insulin receptor (IR) expression in the pathogenesis of diabetes was examined, since it has been shown that the IR is a chemotactic receptor capable of directing cell movement in response to insulin. Using polyclonal antisera to the IR, phenotypic analysis of purified splenic T cells from diabetic mice showed that about 15% of T cells expressed high density IR (IRhigh). In addition, IRhigh T cells were already a dominant phenotype in the insulitis of young prediabetic mice. To determine the ability of IRhigh T cells to transfer diabetes, cells were sorted by flow cytometry before adoptive transfer into young (6- to 8-wk-old) nondiabetic irradiated nonobese mice. Transfer of as few as 3 x 10(6) purified IRhigh T cells alone resulted in rapid onset of insulitis and diabetes, and IRhigh-depleted T cells were essentially unable to passage either insulitis or diabetes. The adoptive transfer of disease was not due to the transfer of activated cells, since removal of IL-2R+ or transferrin R+ cells did not alter diabetes transfer. Therefore, IRhigh T cells are aggressively diabetogenic, suggesting that increased IR expression may provide a mechanism for delivering potentially autoreactive T cells to the islet, regardless of their activation state.
McInerney
M F
MF
Department of Medicinal and Biological Chemistry, University of Toledo, OH 43606, USA.
Flynn
J C
JC
Goldblatt
P J
PJ
Najjar
S M
SM
Sherwin
R S
RS
Janeway
C A
CA
D000818:Animals; D000906:Antibodies; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology / Q000276:immunology* / Q000378:metabolism*; D005260:Female; D007116:Immunization, Passive; D007515:Islets of Langerhans / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D011972:Receptor, Insulin / Q000276:immunology / Q000378:metabolism*; D013154:Spleen / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*
D000906:Antibodies; D011972:Receptor, Insulin