Circulating lymphocyte subpopulations in juvenile insulin-dependent diabetes

Abstract

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.

Peripheral blood T-cell subsets studied by monoclonal antibodies in Type 1 (insulin-dependent) diabetes: effect of blood glucose control

“…Monoclonal antibodies used were specifically directed against T4 'helper' cells (Leu-3a, Becton Dickinson), against T8 'suppressor/cytotoxic' cells (BL]5, kindly provided by J. Brochier, Lyon, France) and against HLA-D/DR-bearing cells (BL2, J. Brochier); the detection of positive cells by each monoclonal antibody was achieved by a immunofluorescence method using fluoresceinated class-specific goat anti-mice immunoglobulins [12]. Total T cells were enumerated using classical E-rosettes and Ig-bearing B- Results expressed as mean _+ SD cells were detected by membrane immunofluorescence [6]. Finally, monocyte contamination was assessed using peroxidase staining.…”

“…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].…”

“…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.…”

High Insulin Requirements and Poor Metabolic Control do not Modify the Expression, Regulation and PKC Mediated Activation of the p21ras Pathway in PBMC from Type II Diabetic Patients

“…[1,14,151 In addition, a variety of signaling defects has been reported in PBMC from type II patients [16-18I and hyperglycemia has been implicated as a reversible cause of aberrant T cell activation in diabetic patients. [19] [21,221 and by the recent demonstration that ras transformed brown adipocytes developed insulin resistance due to a signaling defect up-stream of ras, without decreasing the activity of p21ras down-stream elements. [23] It is also supported by our previous demonstration in type I patients and pre-diabetic animals of a restricted defect in the activation of p21ras located up-stream of PKC p21ras complex and the cell membrane.…”

The effects of 3-hydroxybutyrate and glucose on human T cell responses toCandida albicans

“…In a study of 26 non-diabetic patients with chronic mucocutaneous candidosis, 16 showed abnormal T cell function in response to Candida antigen as assessed by 3 criteria: (i) ability to mount a delayed hypersensitivity response; (ii) ability to produce migration inhibitory factor; or (iii) transformation of lymphocytes in vitro [5]. The status of T cells in diabetes is controversial: although mitogen-316 stimulated T cell proliferation has been reported to be suppressed in diabetes [6][7][8], stimulation with various antigens in vitro has shown no difference between diabetic and control subjects [9,10]. A possible reason for these different results is that antigen stimulated T cells are usually cultured for six days compared to three or four days for mitogen stimulated cultures, prolonged culture in standard medium containing 11 mmol 1-1 glucose might overcome defects acquired by T ceils of diabetic patients in vivo.…”