The relationship between peripheral T cell reactivity to insulin, clinicalremissions and cytokine production in type 1 (insulin-dependent) diabetes mellitus
A. Mayer et al., The relationship between peripheral T cell reactivity to insulin, clinicalremissions and cytokine production in type 1 (insulin-dependent) diabetes mellitus, J CLIN END, 84(7), 1999, pp. 2419-2424
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.