The relationship between peripheral T cell reactivity to insulin, clinicalremissions and cytokine production in type 1 (insulin-dependent) diabetes mellitus

Antigenic proliferative responses of peripheral blood mononuclear cells (PB MC) to insulin were studied in 44 type 1 new-onset diabetic subjects. Of th em, 14 (32%) had a stimulation index (greater than or equal to 3) above the mean + 3 SD of 39 healthy controls and of 7 of 15 (47%) diabetic patients of long duration (P = 0.001). Responses to insulin were not dictated by spe cific major histocompatibility complex class II association and were not ob served in normal subjects with diabetes-associated human leukocyte antigen- DR/DQ alleles. Whereas no relation of PBMC reactivity with insulin autoanti bodies was found, there was a positive correlation with the presence of at least one of the four autoantibodies tested and with IA-2 antibody. An inte resting finding was that the proportion of patients with subsequent low ins ulin requirement, up to 24 months, was significantly higher in patients who showed PBMC reactivity to insulin (8 of 8) than in those who did not (10 o f 24, 42%; P = 0.004). The former had a higher mean stimulation index than the latter (3.3 +/- 2.6 vs. 1.5 +/- 0.6; P = 0.006). Furthermore, interleuk in-4 (IL-4) production was lower in type 1 diabetic patients who proliferat ed to insulin than in those who did not (23 +/- 15 vs. 64 +/- 47 pg/mL; P = 0.04), but interferon-gamma, IL-2, and IL-10 productions were similar. In conclusion, these results suggest that proliferation to insulin may reflect the presence of an higher residual beta-cell mass.