High density insulin receptor-positive diabetogenic T lymphocytes in nonobese diabetic mice are memory cells

Our previous work examining the importance of insulin receptor (IR) express ion on T cells has demonstrated that when T cells from nonobese diabetic mi ce were sorted into populations expressing a high (IRHigh) and a low (IRLow ) density of IR, IRHigh T cells rapidly transferred insulitis and diabetes. We have further characterized IRHigh T cells. Both CD4(+) and CD8(+) cells were detected in the IRHigh T cell population, but IRHigh expression was d etected predominantly on CD4(+) cells. IRHigh T cells were polyclonal for T CR VP-chain expression. By 3 color flow cytometric analysis, virtually all IRHigh T cells expressed low or negligible levels of CD62L (CD62L(Low/-)) a nd high levels of CD44 (CD44(High)). The lack of IL-2 receptor and transfer rin receptor expression as seen previously, together with the CD62L(Low/-) CD44(High) phenotype suggests that IRHigh T cells are memory cells. However , since only about one quarter of all of the CD62L(Low/-) or CD44(High) T c ells were also IRHigh, the IRHigh phenotype defines a subpopulation of memo ry T cells that are aggressively diabetogenic.