Regulatory T cells in type 1 diabetic patients with autoimmune chronic atrophic gastritis

Abstract

Type A chronic atrophic gastritis (CAG) is increased in type 1 diabetic patients (DM1). To address this issue, we determined and analyzed the number of peripheral blood regulatory T cells (Tregs) in 15 DM1-CAG patients, 15 DM1 patients without associated autoantibodies (DM1) and 15 healthy controls by flow cytometry and compared gastric Tregs expression (CD4+Foxp3+/CD4+) in DM1-CAG patients with that observed in 10 control Helicobacter pylori CAG-infected biopsies. The percentage of peripheral Tregs was higher in DM1-CAG patients compared to DM1 and controls (CD4+Foxp3+: 7.67 +/- 1.91% vs. 5.38 +/- 1.57% and 5.65 +/- 1.76%, P < 0.001, respectively), with no differences between DM1 and controls. Gastric mucosal Tregs were higher in H. pylori CAG than in DM1-CAG patients (31.31 +/- 5.52% vs. 7.68 +/- 3.70%; P < 0.001). Data suggest that Tregs are stimulated in patients with more than one autoimmune disease (DM1 + CAG) in an ineffectual attempt to control autoimmune response and that the number of Tregs in gastric mucosa implicated in the chronification of gastritis differs according to the etiology.

Type 1 Diabetic Children and Siblings Share a Decrease in Dendritic Cell and Monocyte Numbers but are Differentiated by Expansion of CD4+T Cells Expressing IL-17

“…lo/-and CD4 + Foxp3 + T cells between the three groups, a finding similar to other studies investigating diabetic subjects [11][12][13]. However, our study identified a strong association between the age at time of sampling and age of diagnosis and the proportion of CD4…”

“…This finding of decreased MDC and PDC numbers in both recent-onset and established T1D subjects was interpreted as a primary manifestation of T1D [3]. A decreased number of T Reg cells has also been reported in children with recentonset TID, adults with established T1D and in the offspring of parents who carry the high risk human leukocyte antigen (HLA) alleles [9,10], Other studies have found comparable T Reg cell populations in adults with established T1D and HLA /age-matched controls [11][12][13]. These differences between the reported blood DC and T Reg numbers may result from different experimental conditions (e.g.…”

“…These differences between the reported blood DC and T Reg numbers may result from different experimental conditions (e.g. study of erythrocyte-lysed fresh blood samples [3,13] versus Ficoll-density gradient isolated blood mononuclear cells [7][8][9][10][11][12] or superficial analyses (e.g. restricted surface markers for identifying DC and T Reg cells, constraints of three-to four-color flow cytometry).…”

Cutting Edge: Increased IL-17–Secreting T Cells in Children with New-Onset Type 1 Diabetes

“…In previous studies, where the data have been inconsistent regarding the proportion of Tregs in T1D subjects (16)(17)(18)(19)(20), the differences seen may have been the result of using CD25 alone as a marker of Tregs (18), using a control population older than that of the T1D group (21), and using a less specific FOXP3 Ab clone (PCH101) that precluded greater discrimination of FOXP3 high versus FOXP3 low cells (22). Given these differences, preceding studies that assessed FOXP3 + T cells in T1D subjects would not easily have identified the CD45RA 2…”

Mechanisms of Immunological Tolerance Disruption

“…Экспериментальные иссле-дования также свидетельствуют о негативной корреляции между уровнем Treg-лимфоцитов и активностью заболевания при аутоиммун-ных расстройствах, включая РА [Kawashiri et al, 2011;Kim et al, 2012], РС Saresella et al, 2008], СКВ [Habibagahi et al, 2011] и др. По данным ряда исследователей, уровень Tregs может не отличаться от контро-Tregs может не отличаться от контро-может не отличаться от контро-ля, или даже их содержание в крови может быть увеличено [Alonso et al, 2009;Nie et al, 2013], однако наряду с этим отмечается снижение супрессорной функции этих клеток Mikulkova et al, 2011;. Количественный дефект Тreg-клеток может проявляться вслед-ствие снижения уровня экспрессии FOXP3, что было показано у больных РА [Hun et al, 2008] и РС .…”