High Density Insulin Receptor-Positive Diabetogenic Tlymphocytes in Nonobese Diabetic Mice are Memory Cells

Abstract

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

Keywords:

• Rodent
• T lymphocytes
• FACS
• Cell surface molecules
• insulin receptor