A Pilot Study Showing Associations Between Frequency of CD4(+) Memory Cell Subsets at Diagnosis and Duration of Partial Remission in Type 1 Diabetes

Overview

Journal Clin Immunol

Specialty Allergy & Immunology

Date 2016 Apr 27

PMID 27114212

Citations 16

Authors

Rosita Moya

Hannah Kathryn Robertson

Dawson Payne

Aditi Narsale

Jim Koziol

Joanna Davida Davies

Affiliations

Soon will be listed here.

Abstract

In some patients with type 1 diabetes the dose of insulin required to achieve euglycemia is substantially reduced soon after diagnosis. This partial remission is associated with β-cell function and good glucose control. The purpose of this study was to assess whether frequencies of CD4(+) T cell subsets in children newly diagnosed with type 1 diabetes are associated with length of partial remission. We found that the frequency of CD4(+) memory cells, activated Treg cells and CD25(+) cells that express a high density of the IL-7 receptor, CD127 (CD127(hi)) are strongly associated with length of partial remission. Prediction of length of remission via Cox regression is significantly enhanced when CD25(+) CD127(hi) cell frequency is combined with either Insulin Dependent Adjusted A1c (IDAA1c), or glycosylated hemoglobin (HbA1c), or C-peptide levels at diagnosis. CD25(+) CD127(hi) cells do not express Foxp3, LAG-3 and CD49b, indicating that they are neither Treg nor Tr1 cells.

Citing Articles

Role of EP4 factor in paediatric type 1 diabetes mellitus: a comprehensive review focusing on the honeymoon period.

Taheri F, Panahi N, Vahidi A, Asadi M, Amoli M, Goharifar N Pediatr Endocrinol Diabetes Metab. 2025; 30(4):227-246.

PMID: 39963060 PMC: 11809557. DOI: 10.5114/pedm.2024.146686.

TGF-β-mediated crosstalk between TIGIT Tregs and CD226CD8 T cells in the progression and remission of type 1 diabetes.

Zhong T, Li X, Lei K, Tang R, Deng Q, Love P Nat Commun. 2024; 15(1):8894.

PMID: 39406740 PMC: 11480485. DOI: 10.1038/s41467-024-53264-8.

Approaches to Measuring Beta Cell Reserve and Defining Partial Clinical Remission in Paediatric Type 1 Diabetes.

Kennedy E, Hawkes C Children (Basel). 2024; 11(2).

PMID: 38397298 PMC: 10887271. DOI: 10.3390/children11020186.

Combined unsupervised and semi-automated supervised analysis of flow cytometry data reveals cellular fingerprint associated with newly diagnosed pediatric type 1 diabetes.

Bechi Genzano C, Bezzecchi E, Carnovale D, Mandelli A, Morotti E, Castorani V Front Immunol. 2022; 13:1026416.

PMID: 36389771 PMC: 9647173. DOI: 10.3389/fimmu.2022.1026416.

Clinical Outcomes of Fetal Stem Cell Transplantation in Type 1 Diabetes Are Related to Alternations to Different Lymphocyte Populations.

Tootee A, Nikbin B, Nasli Esfahani E, Arjmand B, Aghayan H, Qorbani M Med J Islam Repub Iran. 2022; 36:34.

PMID: 36128298 PMC: 9448473. DOI: 10.47176/mjiri.36.34.

References

Yao Y, Vent-Schmidt J, McGeough M, Wong M, Hoffman H, Steiner T . Tr1 Cells, but Not Foxp3+ Regulatory T Cells, Suppress NLRP3 Inflammasome Activation via an IL-10-Dependent Mechanism. J Immunol. 2015; 195(2):488-97. DOI: 10.4049/jimmunol.1403225. View

McGinty J, Chow I, Greenbaum C, Odegard J, Kwok W, James E . Recognition of posttranslationally modified GAD65 epitopes in subjects with type 1 diabetes. Diabetes. 2014; 63(9):3033-40. PMC: 4392921. DOI: 10.2337/db13-1952. View

Abdul-Rasoul M, Habib H, Al-Khouly M . 'The honeymoon phase' in children with type 1 diabetes mellitus: frequency, duration, and influential factors. Pediatr Diabetes. 2006; 7(2):101-7. DOI: 10.1111/j.1399-543X.2006.00155.x. View

Rameshwar P, Chang V, Gascon P . Implication of CD44 in adhesion-mediated overproduction of TGF-beta and IL-1 in monocytes from patients with bone marrow fibrosis. Br J Haematol. 1996; 93(1):22-9. DOI: 10.1046/j.1365-2141.1996.4631004.x. View

Lin W, Haribhai D, Relland L, Truong N, Carlson M, Williams C . Regulatory T cell development in the absence of functional Foxp3. Nat Immunol. 2007; 8(4):359-68. DOI: 10.1038/ni1445. View

Kretschmer K, Apostolou I, Hawiger D, Khazaie K, Nussenzweig M, von Boehmer H . Inducing and expanding regulatory T cell populations by foreign antigen. Nat Immunol. 2005; 6(12):1219-27. DOI: 10.1038/ni1265. View

Gagliani N, Magnani C, Huber S, Gianolini M, Pala M, Licona-Limon P . Coexpression of CD49b and LAG-3 identifies human and mouse T regulatory type 1 cells. Nat Med. 2013; 19(6):739-46. DOI: 10.1038/nm.3179. View

Fontenot J, Gavin M, Rudensky A . Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nat Immunol. 2003; 4(4):330-6. DOI: 10.1038/ni904. View

Skowera A, Ladell K, McLaren J, Dolton G, Matthews K, Gostick E . β-cell-specific CD8 T cell phenotype in type 1 diabetes reflects chronic autoantigen exposure. Diabetes. 2014; 64(3):916-925. PMC: 4557541. DOI: 10.2337/db14-0332. View

10.

Bollyky P, Lord J, Masewicz S, Evanko S, Buckner J, Wight T . Cutting edge: high molecular weight hyaluronan promotes the suppressive effects of CD4+CD25+ regulatory T cells. J Immunol. 2007; 179(2):744-7. DOI: 10.4049/jimmunol.179.2.744. View

11.

Zhang X, Li X, Xiao X, Sun R, Tian Z, Wei H . CD4(+)CD62L(+) central memory T cells can be converted to Foxp3(+) T cells. PLoS One. 2013; 8(10):e77322. PMC: 3796486. DOI: 10.1371/journal.pone.0077322. View

12.

Bober E, Dundar B, Buyukgebiz A . Partial remission phase and metabolic control in type 1 diabetes mellitus in children and adolescents. J Pediatr Endocrinol Metab. 2001; 14(4):435-41. DOI: 10.1515/jpem.2001.14.4.435. View

13.

Dendrou C, Plagnol V, Fung E, Yang J, Downes K, Cooper J . Cell-specific protein phenotypes for the autoimmune locus IL2RA using a genotype-selectable human bioresource. Nat Genet. 2009; 41(9):1011-5. PMC: 2749506. DOI: 10.1038/ng.434. View

14.

Long S, Buckner J, Greenbaum C . IL-2 therapy in type 1 diabetes: "Trials" and tribulations. Clin Immunol. 2013; 149(3):324-31. DOI: 10.1016/j.clim.2013.02.005. View

15.

Gavin M, Rasmussen J, Fontenot J, Vasta V, Manganiello V, Beavo J . Foxp3-dependent programme of regulatory T-cell differentiation. Nature. 2007; 445(7129):771-5. DOI: 10.1038/nature05543. View

16.

Shevach E, Davidson T, Huter E, Dipaolo R, Andersson J . Role of TGF-Beta in the induction of Foxp3 expression and T regulatory cell function. J Clin Immunol. 2008; 28(6):640-6. DOI: 10.1007/s10875-008-9240-1. View

17.

Marie J, Letterio J, Gavin M, Rudensky A . TGF-beta1 maintains suppressor function and Foxp3 expression in CD4+CD25+ regulatory T cells. J Exp Med. 2005; 201(7):1061-7. PMC: 2213134. DOI: 10.1084/jem.20042276. View

18.

Mortensen H, Hougaard P, Swift P, Hansen L, Holl R, Hoey H . New definition for the partial remission period in children and adolescents with type 1 diabetes. Diabetes Care. 2009; 32(8):1384-90. PMC: 2713624. DOI: 10.2337/dc08-1987. View

19.

Buyukgebiz A, Cemeroglu A, Bober E, Mohn A, Chiarelli F . Factors influencing remission phase in children with type 1 diabetes mellitus. J Pediatr Endocrinol Metab. 2002; 14(9):1585-96. DOI: 10.1515/jpem.2001.14.9.1585. View

20.

Bacchetta R, Bigler M, Touraine J, Parkman R, Tovo P, Abrams J . High levels of interleukin 10 production in vivo are associated with tolerance in SCID patients transplanted with HLA mismatched hematopoietic stem cells. J Exp Med. 1994; 179(2):493-502. PMC: 2191349. DOI: 10.1084/jem.179.2.493. View