Kd-NRP-V7-SAP and Kd-IGRP-SAP delayed onset of diabetes but not Kd-INsB-SAP or Dd-DMK-SAP. (a,c,d) Ten NOD mice per group were given 3 i.v. injections of the indicated toxic tetramer over 2 weeks beginning at 8 weeks of age. A Kaplan-Meier curve is shown above with diabetes incidence as the dependent variable. (a) Kd-NRP-SAP treatment significantly reduced diabetes incidence (logrank test, P = 0.04). Mean time to onset, PBS = 16.5 weeks, Kd-NRP-SAP = 24.5 weeks (b) NRP-V7-specific CD8+ T cells are a subset of the IGRP-specific CD8+T cells. Lymphocytes were isolated from the islets of a NOD mouse and stained with anti-CD8 PerCp, anti-CD3 AF488 and anti-CD19 Pacific Blue antibodies in addition to two tetramers, Kd-NRP-V7-SA-AF647 and Kd-IGRP-SA-PE. Cells were analyzed by flow cytometry. The CD8+CD3+T cells are shown in the dot plot. (c) Kd-IGRP-SAP but not Kd-DMK-SAP significantly delayed onset of diabetes (logrank test, P = 0 .02). Mean time to onset, PBS = 18 weeks, Kd-IGRP-SAP = 32 weeks, and Dd-DMK-SAP = 16 weeks (d) Kd-INsB-SAP did not reduce diabetes incidence. Mean time to onset, PBS = 14 weeks, Kd-INsB-SAP = 16.5 weeks. Blood ALT( alanine aminotransferase) levels (indicative of liver damage) measured after each dose of toxic tetramer did not rise above 350, consistent with mild transient effects.