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Circulating lymphocytes from 39 juvenile insulin dependent diabetics of recent onset were studied by six membrane marker techniques and mitogen stimulation. Well controlled (n = 14) were grouped separately from poorly controlled (n = 25) patients. The total lymphocyte counts were not different from 50 control subjects. The percentage of T-cells detected by erythrocyte rosettes and B-cells detected by erythrocytes--antibody--complement rosettes was significantly decreased only in poorly-controlled diabetics (64.1 +/- 1.3 and 9.7 +/- 1.8, vs 71.0 +/- 1.0 and 15.3 +/- 0.6 in controls). Cells bearing receptors for the Fc fragment of IgG immunoglobulins were decreased in both groups. Mitogen stimulation was not different from controls but was significantly lower in poorly controlled than in well controlled diabetics. Optimal blood glucose control for 5 +/- 2 days using an external artificial pancreas led to a rapid normalisation of membrane marker values and mitogen responsiveness of lymphocytes from previously poorly controlled diabetics. Separate in vitro experiments showed that glucose had an inhibitory effect on mitogen stimulation at concentrations greater than or equal to 8.3 mmol/l and on T- and B-lymphocyte numbers at concentrations greater than or equal to 55.6 mmol/l. DL 3-hydroxybutyrate tested at 17.1 and 34.2 mmol/l only depressed mitogen responsiveness. Such results suggest a rapidly reversible T-cell defect closely linked to the existing metabolic disturbances.

Summary. Peripheral T lymphocyte subsets were investigated, using monoclonal antibodies, in 14 patients with acute diabetes of duration less than 1 month (before insulin treatment) and after prolonged strict blood glucose control, and also in 40 healthy volunteers. At the time of diagnosis, the percentage total T cells was decreased (67.6 ___ 8.4 versus 72.8 + 6.6%), but T4 'helper' cells and T8 'suppressor/cytotoxic' cells were in the normal range. The T4/T8 ratio was not significantly higher than in the control group and B-cell percentages were increased (IgS: 18.3 _+ 7.1 versus 12.4 + 4.9%). The second T cell enumeration, performed after sustained normoglycaemia, showed a normal total T cell percentage and a decrease in the T4/T8 ratio depending on a decrease of T4 cells (38.3_ 12.8 versus 49.3 + 13.4), without any change of T8 lymphocytes; B cells remained elevated. These results suggest that insulin deficiency/metabolic derangement was responsible for an imbalance of circulating lymphocytes and underlines the importance of metabolic control in the assessment of such immunological parameters.Key words: Monoclonal antibody, Type 1 diabetes, T lymphocyte subsets, metabolic control.Numerous studies support the hypothesis that autoimmunity is involved in the pathogenesis of Type I (insulin-dependent) diabetes mellitus. The presence of the anti-islet antibodies [1] and insulitis [2] at the early phase of the disease, the characteristic association between HLA antigens and diabetes [3], and the role of environmental factors at the onset of the disease [4] suggest that a genetically determined immune reaction is involved in the B-cell lysis. Several studies concerning cell-mediated immunity have shown a lymphocytic sensitization against pancreatic antigens in recent Type 1 diabetes [5] an altered lymphocyte response to T-cell mitogens in poorly controlled diabetes [6] and a lowered suppressor cell activity at the onset of the disease [7]. Studies concerning the enumeration of circulating blood lymphocytes have been conflicting, showing a reduction of peripheral T lymphocytes [8], an excess of B lymphocytes [9], or a normal lymphocyte population [10]. These discrepancies may be explained by methodological considerations, patient selection, or degree of metabolic control, as reported previously [6]. More recently, T lymphocyte subpopulations have been investigated using monoclonal antibodies, but results still remain conflicting.In an attempt to define these differences, we have re-evaluated the influence of metabolic control on the phenotype of circulating blood lymphocytes and specially of T lymphocyte subsets using monoclonal antibodies. Subjects and methods SubjectsWe studied 14 patients (seven males and seven females; median age 18 years; range 6-40 years) with acute diabetes with symptoms of less than t month before the initiation of insulin treatment, and 8-10 days later, after a 3-day intravenous insulin infusion to achieve sustained normoglycaemia; the insulin infusion was performed using an open loop system...

We still cannot explain why the human fetus, an allograft, is not rejected by the pregnant mother, particularly since humoral and cell-mediated responses have been demonstrated against the paternal haplotype (1). There is, furthermore, some evidence of increased suppressor cell activity in the human fetus (2).Rheumatoid arthritis (RA) is a chronic rheumat-