Immunoregulatory T-lymphocyte subset deficiency in newly diagnosed type 1 (insulin-dependent) diabetes mellitus

Abstract

Humoral and cell-mediated disorders in Type 1 (insulin-dependent) diabetes suggest that an imbalance of immunoregulatory T-cell subsets exists. In 23 newly diagnosed (onset less than 3 months) and 21 long-standing Type 1 diabetic patients, T lymphocyte subsets were analyzed using monoclonal antibodies (OKT3, OKT4, OKT8, OKM1). The newly diagnosed patients showed a reduction with a significant difference from healthy controls in total T cells (OKT3+: 58.1 +/- 8.5% versus 70.7 +/- 8.0%), helper/inducer cells (OKT4+: 33.8 +/- 7.0% versus 47.1 +/- 8.3%), suppressor/cytotoxic cells (OKT8+: 18.5 +/- 7.3% versus 32 +/- 6.8%) and monocytes (OKM1+: 11.5 +/- 3.8% versus 19.9 +/- 5.2%) (p less than 0.001). The long-standing diabetic patients also revealed a low number of immunoregulatory T cells compared with control subjects, although to a lesser extent (p less than 0.01-0.05). The helper/suppressor ratio (OKT4+/OKT8+) was higher in newly diagnosed patients than in control subjects (2.2 +/- 1.3 versus 1.5 +/- 0.3; p less than 0.02). When compared with 95% tolerance limits in the control subjects, the reduction of OKT8+ cells in the newly diagnosed diabetic patients appeared more marked: the mean (18.5%) coincided with the lower limit of normal subjects (18.3%). Ten of the newly diagnosed Type 1 diabetic patients had a value below the normal lower limit. Out data point to the occurrence of different immunoregulatory abnormalities in newly diagnosed Type 1 diabetic patients, especially in OKT8+ and OKT4+ cells. The imbalance in T lymphocyte subsets is further proof of the role of cellular autoimmunity in the pathogenesis of the early phases of Type 1 diabetes.