NRP-V7–specific T cells in peripheral blood can be used to predict diabetes development. (a) Mean proportion (± SEM) of NRP-V7 tetramer-positive CD8⁺ B220^– cells in peripheral blood of mice that developed diabetes (filled circles; n = 13) versus mice that remained nondiabetic to 32 weeks of age (open squares; n = 5). Mice from different litters were analyzed in two groups, beginning at 6 (n = 6) or 9 weeks of age (n = 12). Most diabetic mice were removed from the study after 21 weeks of age. The difference in NRP-V7 tetramer-positivity between diabetic and nondiabetic mice was significant for every time point from 9 to 16 weeks of age (bar; P < 0.001). For diabetic animals, the differences between NRP-V7 tetramer-positive peaks (*) and the time points before and after the peak were also significant (P < 0.001). (b) Accumulation of NRP-V7 tetramer-positive cells in peripheral blood of diabetic (open circles; n = 13) and nondiabetic (open squares; n = 5) mice from 9 to 16 weeks of age. Weekly measurements of NRP-V7 tetramer-positive cells were summed cumulatively and expressed as a mean ± the 95% confidence interval (shading). (c) Representative data from individual mice showing the proportion of NRP-V7 tetramer-positive cells in peripheral blood (filled circles) along with blood glucose (solid line, no symbols). Glucose normalization following hyperglycemia was due to insulin treatment. Arrows indicate the point at which mice had accumulated 0.75% NRP-V7 tetramer-positive cells, predictive of diabetes development. Time points where NRP-V7 tetramer staining exceeded 0.50% (*) or 1.00% (+) are indicated along with the 0.50% threshold (dashed line).