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O Simell

Publications and source records attributed to O Simell.

At least 127 records · Page 7Linked to original sources
PubMed1997

Stage-specific degeneration of germ cells in the seminiferous tubules of non-obese diabetic mice.

The cause of fertility problems in insulin-dependent diabetes is largely unknown. To evaluate the role of autoimmunity-associated phenomena in the testis as a possible cause of the derangement in spermatogenesis, the stage-specific apoptosis of germ cells in the insulitis phase of pre-diabetes was quantified in the testes of non-obese diabetic (NOD) mice. The seminiferous epithelium of normal BALB/c and NOD mice contained cells positive for in-situ end-labelling (ISEL) of DNA. ISEL-positive germ cells formed clusters in the seminiferous epithelium of the NOD mice in marked contrast to the seminiferous epithelium of the BALB/c mice, which contained only individual cells positive for ISEL. ISEL-positive cells were present in the basal and luminal compartments of the epithelium. Ultrastructural analysis and demonstration of externalized phosphatidyl serine confirmed that the cells were undergoing apoptosis. The ultrastructurally apoptotic cells included spermatogonia, spermatocytes and spermatids. In cytological squash preparations of segments of seminiferous tubules from NOD mice aged 17-20 weeks, the number of ISEL-positive cells/mm tubule was significantly lower in segments at stages I-II of the seminiferous epithelial wave but higher at stages III-IV in comparison to BALB/c mice. The numbers of ISEL-positive cells/mm tubule in the other stages were similar in the two strains of mice. Analysis of 32P-3'-end labelled DNA from the testes showed that the BALB/c mice had relatively more DNA fragmentation than did the NOD mice. These data suggest that autoimmune insulitis in the NOD mice is associated with increased amounts and abnormal stage distribution of apoptosis in the seminiferous epithelium, resulting in derangement of spermatogenesis.

Animals↗
PubMed1997

Lysinuric protein intolerance (LPI) gene maps to the long arm of chromosome 14.

Lysinuric protein intolerance (LPI) is an autosomal recessive disease characterized by defective transport of cationic amino acids and by hyperammonemia. Linkage analysis in 20 Finnish LPI families assigned the LPI gene locus to the proximal long arm of chromosome 14. Recombinations placed the locus between framework markers D14S72 and MYH7, a 10-cM interval in which the markers D14S742, D14S50, D14S283, and TCRA showed no recombinations with the phenotype. The phenotype was in highly significant linkage disequilibrium with markers D14S50, D14S283, and TCRA. The strongest allelic association obtained with marker TCRA, resulting in a P(excess) value of .98, suggests that the LPI gene locus lies in close proximity to this marker, probably within a distance of < 100 kb.

Adult↗
PubMed1997

Intake and indicators of iron and zinc status in children consuming diets low in saturated fat and cholesterol: the STRIP baby study. Special Turku Coronary Risk Factor Intervention Project for Babies.

A low-fat diet may predispose children to low meat consumption, low iron intake, and iron deficiency. In the randomized prospective Special Turku Coronary Risk Factor Intervention Project for Babies (STRIP baby study), families of 540 children were counseled to reduce exposure of children > 7 mo of age to known environmental risk factors for coronary heart disease. The control group consisted of 522 children whose families received no specific counseling concerning dietary fat. Iron and zinc intakes of 79 children aged 3-4 y (40 in the intervention group and 39 in the control group) were assessed with 4-d food records. The children in the intervention group consumed less saturated fat than those in the control group and had continuously higher ratios of dietary polyunsaturated to saturated fatty acids. Mean (+/- SD) daily iron intakes in the intervention and control groups were 8.8 +/- 4.2 mg and 8.6 +/- 2.8 mg, respectively. Laboratory findings in the intervention and control groups, respectively, were as follows: hemoglobin, 123 +/- 8 and 122 +/- 7 g/L; mean cell volume, 81.8 +/- 2.9 and 81.7 +/- 3.2 fL; mean corpuscular hemoglobin, 28.1 +/- 1.3 and 27.8 +/- 1.4 pg; ferritin, 21.8 +/- 11.6 and 19.2 +/- 12.4 microg/L; transferrin, 2.90 +/- 0.30 and 2.85 +/- 0.29 g/L; and transferrin receptor, 2.34 +/- 0.46 and 2.29 +/- 0.39 mg/L. There were no significant differences between the groups. Daily zinc intakes were 7.5 +/- 1.2 mg in the intervention group and 7.4 +/- 1.3 mg in the control group; respective serum zinc concentrations were 11.2 +/- 1.9 and 10.5 +/- 1.6 micromol/L (NS). In conclusion, long-term supervised use of a diet low in saturated fat and cholesterol did not influence intake or serum indicators of iron and zinc in children.

C-Reactive Protein↗
PubMed1997

Oral health of 3-year-old children and their parents after 29 months of child-focused antiatherosclerotic dietary intervention in a prospective randomized trial.

A long-term prospective, randomized dietary intervention to prevent exposure of children to the known atherosclerosis risk factors (the STRIP baby project) was started when the age of the children was 7 months. The aim of this substudy was to analyze the oral effects of the dietary intervention in the children and their parents when the children had reached the age of 3 years. Every fifth family of the main study was invited to this substudy (n = 179). Those studied (n = 148) represented well the intervention and the control groups and both genders in terms of intake of saturated fatty acids, the dietary polyunsaturated fatty acid to saturated fatty acid (PUFA/SAFA) ration and serum cholesterol and HDL cholesterol concentrations. Though no difference was found in sucrose consumption between the intervention and the control groups, the intervention children received relatively (in E%) more energy from carbohydrates than the control children (p < 0.005), used absolutely (in g) and relatively (in E%) less fat (p < 0.05) and had a higher PUFA/SAFA ratio in their diet (p < 0.001). Of the 3-year-old children 93% were caries free, and dental decay was a prevalent in the intervention as in the control children. Control children brushed their teeth unassisted more often than the intervention children (p < 0.05). The intervention fathers also received more energy (in E%) from carbohydrates (p < 0.01), the intervention mothers used less fat (p < 0.05) and had a higher PUFA/SAFA ratio in the diet (p < 0.05) than the control fathers and mothers, respectively. Dental and periodontal health of the intervention and control parents (n = 250, 84% attending, mean +/- SD age: 34.2 +/- 54.5 years also showed no differences even though the control parents had more commonly last visited a dentist over 3 years before this examination (p < 0.05). We conclude that a 29-month period of a low-saturated-fat, low-cholesterol but high-carbohydrate diet as advocated in the STRIP baby trial does not seem to have harmful effects on the oral health of the children or their parents. Minor untoward differences had occurred in the dental health behavior of the control children and their parents.

Arteriosclerosis↗
PubMed1997

Salivary cholesterol of healthy adults in relation to serum cholesterol concentration and oral health.

Salivary lipids are mostly glandular in origin, but some are believed to diffuse directly from serum. This diffusion and the role of salivary lipids in oral health have scarcely been studied. Therefore, the serum and saliva cholesterol concentrations and oral health were analyzed in a group of healthy adults (n = 139; 64 men and 75 women; 34.2 +/- 5.2 yrs). Paraffin-stimulated whole saliva was collected, centrifuged (10,000 x g; 30 min, 4 degrees C), and lyophilized, and the cholesterol and other neutral lipids were extracted, separated by thin-layer chromatography, and quantified. The mean +/- SD (range) of saliva cholesterol concentration was 1.20 +/- 0.75 (0.02-5.46) mumol/L, and the saliva cholesterol level of men (1.36 +/- 0.85 mumol/L) was significantly higher than that of women (1.06 +/- 0.64 mumol/L; p < 0.05). Weak positive correlations between saliva and serum cholesterol concentrations and saliva cholesterol and serum non-high-density lipoprotein cholesterol concentrations were found (r = 0.22, p < 0.05; r = 0.28, p < 0.005, respectively). The saliva cholesterol assay detected subjects with high (> or = 6.5 mmol/L) serum cholesterol values, with sensitivity and specificity values of 100% and 29%, respectively. A positive correlation between the body mass index and the level of saliva cholesterol concentration was also found (r = 0.31 p < 0.01). Oral health, microbial counts, or saliva flow rate revealed no differences in subjects with low and high salivary cholesterol level. We conclude that, in healthy adults, saliva cholesterol concentration reflects serum concentration to some extent and can be used to select individuals with high serum cholesterol levels.

Adult↗
PubMed1997

Expression of MxA protein in blood lymphocytes discriminates between viral and bacterial infections in febrile children.

Interferons (IFNs), which are induced by viruses, form an essential part of host's defense systems against viral infections. The antiviral actions of IFNs are mediated by several IFN-inducible gene products, one of which is Mx protein. To evaluate whether MxA protein expression in lymphocytes could function as an indicator of endogenous IFN production in children with acute febrile illness, we analyzed MxA protein levels in peripheral blood lymphocytes by flow cytometry in the acute phase of the disease. Children with a laboratory-confirmed viral infection [respiratory syncytial virus (RSV) in 21, adenovirus in 10, rotavirus in 5, and influenza, herpes simplex, or EBV in 7 other cases] had significantly higher (p < 0.002) MxA protein levels (median fluorescences in different virus groups ranged from 707 to 765) compared with children with a bacterial infection (n = 12, median fluorescence 548). To characterize further MxA protein expression during infections, cells from 41 patients were stimulated in vitro with exogenous IFN-alpha, and the level of MxA protein expression was determined. The rise in MxA staining levels was significantly higher in the group with bacterial infections compared with those with viral infection (p < 0.005), further indicating that the MxA protein levels were already elevated in vivo in patients with viral infections. This study suggests that elevated MxA protein expression levels can be used in the differential diagnosis of bacterial versus viral disease in febrile children.

Adenoviridae Infections↗
PubMed1997

Behavior of 3-year old children in a prospective randomized trial of reduced saturated fat and cholesterol diet since infancy: the STRIP baby project.

Interventions aimed at decreased exposure of children to known atherosclerosis risk factors may have untoward behavioral side effects. We examined how children's behavior or parent's perception of the behavior of the children at 3 years of age was influenced by the intervention in a prospective randomized trial that began in infancy and effectively decreased serum cholesterol concentration. This Special Turku coronary Risk factor Intervention Project for babies (STRIP) began when the infant was 7 months old. Half of 1,062 children received individualized dietary counseling at 1 to 3-month intervals during the first 2 years of age and then half-yearly; the other half had an unrestricted diet. At 3 years of age a standardized questionnaire of the child's behavior was sent to 791 families (76% returned the questionnaire). At the onset of the trial the sociodemographic data of the families and serum lipid values of the intervention and control children were similar. Later, mean serum cholesterol values of the intervention children remained constantly at a level 6% to 10% below the values of the control children. At 3 years of age the parental perceptions of the child's behavior suggested minimal differences between the intervention and control children. The intervention children were slightly less jealous and more active and creative but showed slightly more negative signs of behavior (bed-wetting, problems in falling asleep, fears) than the controls. We conclude that long-term, individualized dietary and lifestyle intervention that begins in infancy slightly influences children's behavior or parent's recognition of the behavior of the children at the age of 3 years.

Journal Article↗
PubMed1997

Regulation of growth of 7- to 36-month-old children by energy and fat intake in the prospective, randomized STRIP baby trial.

OBJECTIVE: To study the fat and energy intakes of children between 7 and 36 months of age with different growth patterns. METHODS: In the Special Turku coronary Risk factor Intervention Project for Babies, children were randomized to intervention (n = 540) and control groups (n = 522) at age 7 months. The intervention was aimed at replacing part of the saturated fat intake with monounsaturated and polyunsaturated fat to reduce children's exposure to high serum cholesterol values. The control children consumed a free diet. Children followed for >2 years (n = 848) were included in the analysis. Five groups of children representing different extreme growth patterns during the first 3 years of life were formed, and their energy and fat intakes were analyzed. Relative weight was defined as deviation of weight in percentages from the mean weight of healthy children of same height and sex, and relative height as deviation of height in SD units from the mean height of healthy children of same age and sex. RESULTS: Relative fat intakes (as percent of energy intake) were similar in children showing highly different height gain patterns. The thin (mean relative weight </= 5%) children consumed more fat (mean, 30% energy [ E%] [SD 7] at 13 months and 33 [4] E% at 24 months) than children with normal growth (27 [5] E% at 13 months and 31 [5] E% at 24 months). The energy intake of the tall (mean relative height >/= 95%) and the obese (mean relative weight >/= 95%) were highest, but weight-based energy intake of the tall (at 2 years, 82 [13] kcal/kg) and the obese (79 [17] kcal/kg) were lower than that of children with normal growth (89 [16] kcal/kg). The thin children consumed relatively more energy than the children with normal growth (at 2 years, 94 [13] kcal/kg and 89 [16] kcal/kg, respectively). Parental height and body mass index and the child's absolute and relative energy intakes predicted the best children's growth patterns. Children with consistently low fat intake grew equally to the children with higher fat intake. CONCLUSIONS: Moderate supervised restriction of fat intake to values 25 to 30 E% is compatible with normal growth.

Arteriosclerosis↗
PubMed1997

Growth until 3 years of age in a prospective, randomized trial of a diet with reduced saturated fat and cholesterol.

OBJECTIVE: Modification of fat intake in childhood may decrease children's future risk for atherosclerosis. Excessive changes in fat intake have been linked with possible growth failure. This study evaluates the effects of a low-saturated fat diet on growth during the first 3 years of life. DESIGN: Half of 1062 healthy infants were randomized at 7 months of age to the intervention group (n = 540) to receive at 1- to 6-month intervals individualized dietary counseling aimed at reducing their exposure to atherosclerosis risk factors. Five hundred twenty-two children served as control children. Growth and serum lipids were measured regularly, and nutrient intakes were analyzed using 3- to 4-day food records at 5- to 12-month intervals. RESULTS: The intervention children consistently consumed slightly less energy than did the control children. The mean fat intake of children in both groups was lower than expected, especially during the first 2 years of life (29.0 [SD, 4.7] percentage of energy intake [E%] and 28.8 [4.1] E% in the intervention and control children, respectively, at 8 months, formula-fed children only). At 13, 24, and 36 months, fat intake in the intervention and control children accounted for 26.2 (6.0) and 27.9 (4.9) E%, 29.9 (5.0) and 32.8 (4.8) E%, and 30.8 (4.9) and 33.2 (4.6) E%, respectively. From 13 to 36 months, the baseline adjusted mean serum cholesterol concentration was lower in the intervention children than the control children (95% confidence interval for the difference between means, -0.27 to -0.12 mmol/L). The true mean of the height of the boys in the intervention group during the trial was at most 0.34 cm more or 0.57 cm less (95% confidence interval), and the weight was at most 0.19 kg more or 0.22 kg less than that of the control boys. The respective values for girls were at most 0.77 cm more or 0.16 cm less and at most 0.42 kg more or 0.04 kg less. The numbers of slim children were similar in both groups. CONCLUSIONS: Fat intake by young children is markedly lower than assumed. A supervised low-saturated fat, low-cholesterol diet has no influence on growth during the first 3 years of life.

Body Height↗
PubMed1997

From pathomechanisms to prediction, prevention and improved care of insulin-dependent diabetes mellitus in children.

Molecular biology, gene technology and immunology have extensively clarified the aetiology and pathogenesis of insulin-dependent diabetes mellitus (IDDM). It is now obvious that the genetic background of the individual, poorly characterized environmental factors and aggressive autoimmune phenomena in a complex interplay contribute to the progression to clinical IDDM. The IDDM risk associated with certain genetic markers, e.g. the risk alleles at various HLA loci, the most strongly predisposing gene region, and the mechanisms that mediate the genetic impact may differ in different populations. In Finland the accumulated genetic evidence is so convincing that two IDDM prevention studies have been initiated. One is a population-based prediction and prevention study, while the other is conducted in first-degree relatives of IDDM patients. Both studies rely on screening of newborn infants for IDDM susceptibility alleles at the HLA-DQB1 locus. Meanwhile, in the clinical care of children with IDDM, the importance of intensified and individualized insulin therapy in prevention of diabetic microangiopathy has become increasingly clear, and should be implemented in the care of most paediatric patients.

Child↗
PubMed1996

Prospective randomized trial of low-saturated-fat, low-cholesterol diet during the first 3 years of life. The STRIP baby project.

BACKGROUND: The long-term consequences of modified fat intake in early childhood are poorly known. The randomized prospective STRIP baby project evaluates the effects of repeated dietary counseling on nutrient intakes and serum lipid values in children 7 months to 3 years old. METHODS AND RESULTS: One thousand sixty-two infants were randomized to intervention and control groups at 7 months of age. The families of the 540 intervention children were counseled to reduce the child's intake of saturated fat and cholesterol but to ensure adequate energy intake. Five hundred twenty-two control children consumed an unrestricted diet. Food records were kept, and serum lipids were measured at 5- to 12-month intervals. Intakes of saturated fat, fat as proportion of energy (E%), and cholesterol were lower in the intervention children than in control children at 13, 24, and 36 months of age. Fat intake by the intervention children decreased from 29 +/- 5 E% at 8 months of age to 26 +/- 6 E% at 13 months and then increased to 30 +/- 5 E% at 24 months and to 31 +/- 5 E% at 36 months. The control children consumed 29 +/- 4 E%, 28 +/- 5 E%, 33 +/- 5 E%, and 33 +/- 5 E% of fat at 8, 13, 24, and 36 months, respectively. The ratio of dietary poly-unsaturated to saturated fats of the intervention children was consistently higher than that of the control children (P < .0001). Baseline adjusted mean serum cholesterol concentration was lower in the intervention children than control children between 13 and 36 months (P < .0001; 95% confidence interval of the difference between the group means, -0.27 to -0.12 mmol/L). The effect was significant only in boys (95% confidence interval, -0.39 to -0.20 mmol/L in boys; -0.21 to 0.01 mmol/L in girls). CONCLUSIONS: Repeated individualized dietary counseling markedly reduces the increase in serum cholesterol concentration that occurs in control children during the first years of life.

Aging↗
PubMed1996

Recirculation and homing of lymphocyte subsets: dual homing specificity of beta 7-integrin(high)-lymphocytes in nonobese diabetic mice.

The beta 7-integrin subunit can pair with two alpha-chains, alpha 4 and alpha E, and is expressed mainly on lymphocytes. As an alpha 4-heterodimer it binds to the mucosal addressin MAdCAM-1, thus acting as a mucosal homing receptor. As an alpha E-heterodimer it binds to E-cadherin and is mainly found on intestinal intraepithelial lymphocytes. Consequently, beta 7 is mostly expressed on lymphocytes of the mucosal immune system. To study the compartmentalization of these cells further we compared the distribution of such lymphocytes in two strains of mice (BALB/c and NOD) and found that the distribution of beta 7-positive lymphocytes among various lymphoid tissues in these strains was very different. In NOD mice a conspicuous population of beta 7-integrin(high) lymphocytes expressing either alpha 4, alpha E, or both, was found in nonmucosal lymphoid tissues such as peripheral lymph nodes (PLNs). They mostly expressed the PLN homing receptor L-selectin, and included both naive and memory cells on the basis of their expression of CD44/pgp-1 and CD45RB, as did the few beta 7(high) lymphocytes in BALB/c PLNs. Their homing to Peyer's patches (PPs) and PLNs was equally effective and the cells homing to PPs and PLNs were equal in their level of L-selectin and alpha 4/beta 7 expression. However, functional studies indicated that their homing to PPs mostly depended on alpha 4/beta 7-integrin, whereas they mainly used L-selectin to home to PLNs. beta 7(high) lymphocytes were found also in circulating blood of unmanipulated NOD mice, and their L-selectin expression was higher than in BALB/c mice. These results show that lymphocytes of the mucosal immune system may also express the peripheral node homing receptor L-selectin during their recirculation and that in NOD mice they frequently retain a dual homing specificity, which leads to their accumulation in nonmucosal tissues.

Animals↗
PubMed1996

Skeletal muscle of patients with gyrate atrophy of the choroid and retina and hyperornithinaemia in ultralow-field magnetic resonance imaging and computed tomography.

Gyrate atrophy of the choroid and retina with hyperornithinaemia (GA), an autosomal recessive disease, affects skeletal muscle in addition to the eye. Muscle biopsy samples show prominent type 2 muscle fibre atrophy. Atrophic fibres also contain accumulations of tubular aggregates in electron microscopy. To evaluate skeletal muscle involvement in detail, the thigh muscles of 7 patients with GA were examined using semi-open conchotome muscle biopsies, computed tomography (CT) and ultralow-field magnetic resonance imaging (MRI) at 0.02 T. In MRI, the T1 and T2 proton relaxation times were measured. Type 2 muscle fibre atrophy was found in all biopsy samples (100%) and tubular aggregates in 6 of the 7 samples studied (87%). The CT density of the muscle tissue was increased in the only child of the study, decreased in 3 elderly subjects, and normal in the remaining 3 patients. Mean T1 relaxation times of the patients were decreased (135 +/- 5 ms) as compared to those of 6 healthy controls (157 +/- 12 ms) (p = 0.002). The T2 relaxation time was slightly increased (40 +/- 3 ms) as compared to the controls (35 +/- 7 ms; not significant, p = 0.3). Our findings suggest that the thigh muscles of the patients with GA universally show changes in CT and MRI studies, but relaxation time measurements gave little additional information on the muscle metabolism.

Adolescent↗
PubMed1996

CD28-CD80/CD86 interactions in testicular immunoregulation.

The expression of two accessory molecules on antigen-presenting cells (APC), the CD80/ B7-1 and CD86/B7-2 antigens, was studied in the testis of normal and non-obese diabetic (NOD) mice. In addition, the effect of CD28 stimulation on suppression of lymphocytes by testicular products was investigated. The testes of 4-week old NOD mice or normal BALB/c mice and the testis of 17-21-week old BALB/c mice contained no CD80 or CD86 expressing cells. In contrast, CD80+ and CD86+ cells were present in the testis of 14-22-week old NOD mice. The CD80+ cells and most of the CD86+ cells were CD11b/CD18 negative. There were some CD11b/CD18+ cells that expressed CD86 weakly. The CD80+ and CD86+ cells were often located adjacent to the vessel walls where a leukocyte not expressing CD80 or CD86 had attached to the endothelium. Some CD80+ and CD86+ cells were present among the interstitial cells. The CD80 and CD86 antigens could not be observed in the same cells as judged from stainings in parallel sections. Stimulation of ConA- or anti-CD3 epsilon-primed peripheral blood or spleen lymphocytes with anti-CD28 was able significantly to antagonize the growth-inhibitory effect of the M(r) > 5 K fraction of testis extracts, but could not abolish it with increasing concentrations of testis extract. The results suggest that T lymphocytes can not be activated locally in the testis of BALB/c and young NOD mice because of the absence of the necessary CD28 ligands, CD80 and CD86, from the APCs and because of the suppression of T lymphocytes by the testicular products. In the testis of older diabetic NOD mice lymphocyte activation may occur because the testes of these mice contain CD80+; CD11b/CD18-, CD86+; CD11b/CD18+ and CD86+; CD11b/CD18- cells and therefore, CD28 co-stimulation, which can antagonize the suppressive effect of testis extract, may occur. The possibilities for clonal anergy in testicular immunoregulation are discussed.

Animals↗
PubMed1996

Effects of prospective, randomized cholesterol-lowering dietary intervention and apolipoprotein E phenotype on serum lipoprotein(a) concentrations of infants aged 7-24 mo.

A high serum lipoprotein(a) [Lp(a)] concentration is associated with increased risk of coronary artery disease. Few external factors are able to markedly modify serum Lp(a) concentrations. The aim of this study was to evaluate how serum Lp(a) concentrations of infants between 7 and 24 mo of age change in a cholesterol-lowering dietary intervention, and to assess the influence of apolipoprotein (apo) E phenotypes on serum Lp(a) concentrations. The intervention children (n=394) had serum cholesterol, non-high-density-lipoprotein cholesterol, and cholesterol corrected for Lp(a)-cholesterol values (P for all <0.001) lower than those of the control children (n=390), but median serum Lp(a) concentrations at the age of 24 mo were not different from those of control children. Serum Lp(a) values differed according to the apo E phenotype as the median Lp(a) values increased from E2/2 to E3/2, E4/2, E3/3, E4/3, and to E4/4 (P for the difference=0.023, Mann-Whitney U test). Our results suggest that apo E phenotype influences serum Lp(a) concentrations noticeably, but the effect of the cholesterol-lowering dietary intervention was not significant in subjects aged 24 mo.

Apolipoproteins E↗
PubMed1996

Appearance of cells expressing CD80 and CD86 costimulatory antigens in the pancreas of nonobese diabetic mice.

The immunopathogenetic mechanisms that lead to type I diabetes in the nonobese diabetic mouse are poorly defined. The immunoregulatory effects of the costimulatory CD80/B7-1 and CD86/B7-2 antigens expressed by the antigen-presenting cells may be crucial for the development of immune responses and their absence may lead to clonal anergy, which is important in the prevention of autoimmune reactivity. To evaluate the role of the CD80 and CD86 antigens in the development of insulin-dependent diabetes mellitus, expression of these antigens in the pancreas of normal and nonobese diabetic mice was studied. The pancreata of normal BALB/c mice and young nonobese diabetic mice contained no CD80- or CD86-positive cells. CD80- and CD86-positive cells appeared in the pancreas of nonobese diabetic mice by 6 weeks of age. Double immunostaining at the age of 12 weeks showed that CD80-positive cells accumulated around the islets of Langerhans but no insulin-containing cells expressed the costimulatory molecules. The morphology of the CD80- and CD86-positive cells was heterogeneous. Many were Mac-1 integrin (CD11b/CD18) positive, suggesting that macrophages expressing the costimulatory antigens are present in the pancreas of all nonobese diabetic mice by 12 weeks of age and that CD80- and CD86-expressing macrophages may be involved in the local regulation of antiislet immune responses.

Animals↗