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) 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. IRHigh T cells were polyclonal for TCR Vbeta-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.
Flynn
J C
JC
Department of Medicinal and Biological Chemistry, University of Toledo, College of Pharmacy, OH 43606, USA.
McInerney
M F
MF
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D018960:Hyaluronan Receptors / Q000378:metabolism; D007156:Immunologic Memory; D019041:L-Selectin / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D016688:Mice, Inbred NOD; D010641:Phenotype; D011972:Receptor, Insulin / Q000378:metabolism*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D011990:Receptors, Transferrin / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*
D018960:Hyaluronan Receptors; D016693:Receptors, Antigen, T-Cell, alpha-beta; D015375:Receptors, Interleukin-2; D011990:Receptors, Transferrin; D019041:L-Selectin; D011972:Receptor, Insulin