Class-II and IL2 receptor positive cells in the pancreas of NOD mice.

The aberrant expression of Class-II molecules on pancreatic B cells in Type 1 (insulin-dependent) diabetes is still a matter of debate. In order to verify if Class-II molecules are expressed on islet cells in the NOD mouse we have studied 21 female mice of different ages (5 to 22 weeks). Serial cryostat pancreas sections were stained with monoclonal rat antibodies against Class-II antigens (P7/7) and the IL2 receptor (AMT-13).

In vivo kinetics of 123I-labelled insulin: studies in normal subjects and patients with diabetes mellitus.

Radioactive tracer techniques using 131I- and 125I-insulin have been applied to study insulin metabolism. A simple method to label human insulin with 123I to a high specific activity is described. We have used this radiotracer to study insulin kinetics in vivo in normal subjects and in two groups of diabetic patients.

Reduced protection against hepatitis B virus following vaccination in patients with type 1 (insulin-dependent) diabetes.

Twenty patients with well controlled Type 1 (insulin-dependent) diabetes of at least 10 years duration and 47 control subjects were vaccinated against the hepatitis B virus using the Hevac B vaccine. The vaccine was administered into the deltoid region on three occasions at intervals of 1 month. Thereafter a fourth dose was given to subjects still negative for antibody to hepatitis B surface antigen (HbsAb).

Normalization of the CD4/CD8 lymphocyte ratio and increased B lymphocytes in long standing diabetic patients following therapy with thymopentin.

A double blind study with thymopentin (TP5) and placebo was performed in 49 patients affected by Type 1 and Type 2 diabetes of long duration characterized by a reduction of the CD4/CD8 (helper/suppressor) lymphocyte ratio. TP5 (50 mg) was administered subcutaneously 3 times weekly for 1 month. Total peripheral lymphocytes and functionally different cell subsets were measured throughout the course of the study.

Detection of activated lymphocytes in endocrine pancreas of BB/W rats by injection of 123I-interleukin-2: an early sign of type 1 diabetes.

Recombinant interleukin-2 (IL2) was labelled with iodine-123 by a modified chloramine T method. The labelled IL2, which had a high specific activity (100-150 microCi/microgram) and retained its capacity for binding to the IL2 receptor on activated lymphocytes in vitro, was injected intravenously into BB/W diabetes-prone and normal rats. Combined immunoperoxidase staining and autoradiography of organ sections revealed that labelled IL2 bound specifically in vivo to IL2-receptor-positive cells in the spleen of both normal and BB/W rats and to activated lymphocytes infiltrating the pancreas of BB/W rats.

In vivo determination of cell mediated immune response in diabetic patients using a multiple intradermal antigen dispenser.

The in vivo cell mediated immune response using a multiple intradermal antigen dispenser (Multitest) was evaluated in 99 diabetic patients (24 Type I and 75 Type II) and in 50 age matched normal subjects. Seven different antigens (tetanus, diphteria, streptococcus, tubercoline, candida, trichophyton, proteus and a glycerine control) were applied in the forearm and the induration for the antigens tested was measured 48 hours later. A score was calculated adding the arithmetic means obtained with each single antigen.

Labelling of interleukin-2 (IL-2) with 123-iodine with retention of its capacity to bind to activated lymphocytes.

Human recombinant interleukin-2 (IL-2) was labelled with Iodine-123 using modified Bolton and Hunter method. Separation from free iodine was performed by gel filtration chromatography using a Sephadex G10 column. HPLC analysis of labelled IL-2 showed that 98% of TCA precipitable radioactivity eluted in a single peak.

Ultrastructure of lymphocyte subsets and of activated lymphocytes in type 1 diabetes as defined by monoclonal antibodies and the immunogold technique.

The ultrastructure of peripheral blood lymphocyte subsets and activated lymphocytes from 5 patients with recent onset insulin-dependent diabetes as identified by monoclonal antibodies (CD4, CD8 and 4F2) and labelled with gold coupled goat anti-mouse IgG are described and depicted. Electron microscopy revealed no differences in appearance between investigated lymphocyte subsets at the single cell level. Activated lymphocytes as defined by an early activation antigen (4F2) do not always have a characteristic appearance nor do they show morphological signs of activation in all cases.

Activation of peripheral blood and intestinal lamina propria lymphocytes in Crohn's disease. In vivo state of activation and in vitro response to stimulation as defined by the expression of early activation antigens.

In the present study the state of activation of either peripheral blood and intestinal lamina propria mononuclear cells in Crohn's disease was defined by investigating the expression of early activation antigens (namely the 4F2 antigen, the transferrin receptor and the interleukin-2 receptor). The expression of 4F2 and T9 antigens was greatly increased--in the peripheral blood and in the intestinal lamina propria whereas the proportion of interleukin-2 receptor bearing cells was much less pronounced. The counts of early activation antigens bearing cells in the lamina propria were quite comparable with those of the autologous peripheral cells.

Why do so few diabetic patients attend dialysis centers in central Italy?

We report the prevalence of end-stage diabetic nephropathy treated by hemodialysis in the Lazio region, which includes the City of Rome, with a total population of over 5 million people. The percentage of diabetic patients among those attending the dialysis centers was 5% (n = 59), which is below the figures reported for both Northern Europe or Southern Italy (Sicily). A higher number (40%) of patients were affected by non-insulin treated diabetes.

The immune response to influenza vaccination in diabetic patients.

The immune response of diabetic patients to influenza vaccination was examined in 31 patients, 10 with Type 1 (insulin-dependent) diabetes and 21 with Type 2 (non-insulin-dependent diabetes), and in 19 normal subjects. Each received a single intramuscular injection of the 3 virus strains (A/Chile,A/Philippines,B/USSR) anti-influenza vaccine recommended by WHO. The antibody titre and the cell-mediated immune response to the 3 virus strains, as evaluated by the generation of activated lymphocytes and enumeration of B lymphocytes, were studied before and 18 h, 72 h and 1, 2, 3 and 6 weeks after vaccination.

White cells transfusion in recent onset type 1 diabetes.

Two HLA-identical brothers developed Type 1 diabetes simultaneously. In the light of present knowledge of the pathogenesis of Type 1 diabetes, immunosuppression was adopted in one brother by means of white cell transfusion from the father. The other brother acted as a control.

A cell surface monoclonal antibody (H366) helps to discriminate human cytotoxic from suppressor T cells.

A study has been undertaken to differentiate T cytotoxic (Tc) and T suppressor (Ts) cell subsets using a monoclonal antibody termed H366 (mouse IgG2b) previously reported to phenotype natural killer and killer (NK/K) cells. Mononuclear cell suspensions from 14 normal subjects were depleted of H366+ cells by means of complement dependent cytotoxicity and the remaining cells were phenotyped with CD8 and CD4 monoclonal antibodies. The effects of depletion with H366 plus complement (C1) on the induction and activity of suppressor and cytotoxic T cells was also examined.

Effect of unlabeled indium oxine and indium tropolone on the function of isolated human lymphocytes.

The purpose of this study was to compare the effect of indium oxine and indium-tropolone complexes (nonradiolabeled) on the function of isolated human lymphocytes. peripheral lymphocytes were obtained from 15 normal volunteers and incubated with indium oxine or indium tropolone according to the standard techniques currently used when cells are radiolabeled for subsequent in vivo studies. The phytohemagglutinin-induced (PHA) lymphocyte transformation and a more specific lymphocyte functional test (the mixed lymphocyte reaction) were performed following incubation with the indium complexes.

Study of the diurnal variation of human lymphocyte subsets.

The diurnal variation of peripheral white cells and in particular of different lymphocyte subsets has been investigated in 11 normal subjects. Monoclonal antibodies (Mab) phenotyping total T lymphocytes (UCHT1), cytotoxic/suppressor (UCHT4), helper T cells (Leu 3a), B lymphocytes (231) and K/NK cells (H25) have been used. In addition to the traditional parametric statistics, the chronobiological approach of cosinor was adopted in order to inferentially obtain the waveform covering the 24-hr period.

Inhibition of the receptor for interleukin-2 induced by carbimazole: relevance for the therapy of autoimmune thyroid disease.

Evidence has been accumulated that the anti-thyroid drugs used in the treatment of Graves' disease may have immunosuppressive properties but the exact mechanism of action is still unclear. In the present study, we have investigated the in vitro effect of carbimazole (CBZ) on the expression of lymphocyte differentiation antigens and on suppressor cell activity. The incorporation of radiolabelled methimazole (35S-MMI, the active metabolite of CBZ) by resting and mitogen stimulated lymphocytes was also investigated.

Imaging of leukocytic infiltration in human cerebral infarcts.

The circulating white blood cells of patients with brain infarction were labelled in vitro with Indium-111 tropolonate; the cells were reinjected to study the inflammatory process by gamma camera imaging. Eight patients with acute cerebral ischemic infarct were studied during the first two weeks after the onset of neurological symptoms. In seven cases a well defined area of increased radioactivity was revealed in the infarcted hemisphere indicating active migration and tracking of labelled leukocytes in cerebral infarct.

Sera from diabetic pregnant women contain reduced titres of inhibiting factors on killer cell activity.

The presence of Fc-receptor-blocking factors in the sera of normal and insulin-dependent diabetic pregnant women was investigated by means of an antibody-dependent cell-mediated cytotoxicity assay. Sera from normal pregnant women induced a significant depression of antibody dependent cell-mediated cytotoxicity when compared with sera from normal and diabetic non-pregnant women (p less than 0.0001; p less than 0.