Glucagon-reactive islet-infiltrating CD8 T cells in NOD mice

Gayatri Mukherjee, Rodolfo J. Chaparro, Jennifer Schloss, Carla Smith, Christopher D. Bando, Teresa P. DiLorenzo

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Summary: Type 1 diabetes is characterized by T-cell-mediated destruction of the insulin-producing β cells in pancreatic islets. A number of islet antigens recognized by CD8 T cells that contribute to disease pathogenesis in non-obese diabetic (NOD) mice have been identified; however, the antigenic specificities of the majority of the islet-infiltrating cells have yet to be determined. The primary goal of the current study was to identify candidate antigens based on the level and specificity of expression of their genes in mouse islets and in the mouse β cell line MIN6. Peptides derived from the candidates were selected based on their predicted ability to bind H-2Kd and were examined for recognition by islet-infiltrating T cells from NOD mice. Several proteins, including those encoded by Abcc8, Atp2a2, Pcsk2, Peg3 and Scg2, were validated as antigens in this way. Interestingly, islet-infiltrating T cells were also found to recognize peptides derived from proglucagon, whose expression in pancreatic islets is associated with α cells, which are not usually implicated in type 1 diabetes pathogenesis. However, type 1 diabetes patients have been reported to have serum autoantibodies to glucagon, and NOD mouse studies have shown a decrease in α cell mass during disease pathogenesis. Our finding of islet-infiltrating glucagon-specific T cells is consistent with these reports and suggests the possibility of α cell involvement in development and progression of disease.

Original languageEnglish (US)
Pages (from-to)631-640
Number of pages10
JournalImmunology
Volume144
Issue number4
DOIs
StatePublished - Apr 1 2015

Fingerprint

Inbred NOD Mouse
Glucagon
T-Lymphocytes
Type 1 Diabetes Mellitus
Islets of Langerhans
Proglucagon
CD8 Antigens
Antigens
Peptides
Autoantibodies
Disease Progression
Epitopes
Insulin
Gene Expression
Cell Line
Serum
Proteins

Keywords

  • Autoantigens
  • Glucagon
  • NOD mice
  • Type 1 diabetes

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Mukherjee, G., Chaparro, R. J., Schloss, J., Smith, C., Bando, C. D., & DiLorenzo, T. P. (2015). Glucagon-reactive islet-infiltrating CD8 T cells in NOD mice. Immunology, 144(4), 631-640. https://doi.org/10.1111/imm.12415

Glucagon-reactive islet-infiltrating CD8 T cells in NOD mice. / Mukherjee, Gayatri; Chaparro, Rodolfo J.; Schloss, Jennifer; Smith, Carla; Bando, Christopher D.; DiLorenzo, Teresa P.

In: Immunology, Vol. 144, No. 4, 01.04.2015, p. 631-640.

Research output: Contribution to journalArticle

Mukherjee, G, Chaparro, RJ, Schloss, J, Smith, C, Bando, CD & DiLorenzo, TP 2015, 'Glucagon-reactive islet-infiltrating CD8 T cells in NOD mice', Immunology, vol. 144, no. 4, pp. 631-640. https://doi.org/10.1111/imm.12415
Mukherjee G, Chaparro RJ, Schloss J, Smith C, Bando CD, DiLorenzo TP. Glucagon-reactive islet-infiltrating CD8 T cells in NOD mice. Immunology. 2015 Apr 1;144(4):631-640. https://doi.org/10.1111/imm.12415
Mukherjee, Gayatri ; Chaparro, Rodolfo J. ; Schloss, Jennifer ; Smith, Carla ; Bando, Christopher D. ; DiLorenzo, Teresa P. / Glucagon-reactive islet-infiltrating CD8 T cells in NOD mice. In: Immunology. 2015 ; Vol. 144, No. 4. pp. 631-640.
@article{a9d487f7a266431ab52524572859d908,
title = "Glucagon-reactive islet-infiltrating CD8 T cells in NOD mice",
abstract = "Summary: Type 1 diabetes is characterized by T-cell-mediated destruction of the insulin-producing β cells in pancreatic islets. A number of islet antigens recognized by CD8 T cells that contribute to disease pathogenesis in non-obese diabetic (NOD) mice have been identified; however, the antigenic specificities of the majority of the islet-infiltrating cells have yet to be determined. The primary goal of the current study was to identify candidate antigens based on the level and specificity of expression of their genes in mouse islets and in the mouse β cell line MIN6. Peptides derived from the candidates were selected based on their predicted ability to bind H-2Kd and were examined for recognition by islet-infiltrating T cells from NOD mice. Several proteins, including those encoded by Abcc8, Atp2a2, Pcsk2, Peg3 and Scg2, were validated as antigens in this way. Interestingly, islet-infiltrating T cells were also found to recognize peptides derived from proglucagon, whose expression in pancreatic islets is associated with α cells, which are not usually implicated in type 1 diabetes pathogenesis. However, type 1 diabetes patients have been reported to have serum autoantibodies to glucagon, and NOD mouse studies have shown a decrease in α cell mass during disease pathogenesis. Our finding of islet-infiltrating glucagon-specific T cells is consistent with these reports and suggests the possibility of α cell involvement in development and progression of disease.",
keywords = "Autoantigens, Glucagon, NOD mice, Type 1 diabetes",
author = "Gayatri Mukherjee and Chaparro, {Rodolfo J.} and Jennifer Schloss and Carla Smith and Bando, {Christopher D.} and DiLorenzo, {Teresa P.}",
year = "2015",
month = "4",
day = "1",
doi = "10.1111/imm.12415",
language = "English (US)",
volume = "144",
pages = "631--640",
journal = "Immunology",
issn = "0019-2805",
publisher = "Wiley-Blackwell",
number = "4",

}

TY - JOUR

T1 - Glucagon-reactive islet-infiltrating CD8 T cells in NOD mice

AU - Mukherjee, Gayatri

AU - Chaparro, Rodolfo J.

AU - Schloss, Jennifer

AU - Smith, Carla

AU - Bando, Christopher D.

AU - DiLorenzo, Teresa P.

PY - 2015/4/1

Y1 - 2015/4/1

N2 - Summary: Type 1 diabetes is characterized by T-cell-mediated destruction of the insulin-producing β cells in pancreatic islets. A number of islet antigens recognized by CD8 T cells that contribute to disease pathogenesis in non-obese diabetic (NOD) mice have been identified; however, the antigenic specificities of the majority of the islet-infiltrating cells have yet to be determined. The primary goal of the current study was to identify candidate antigens based on the level and specificity of expression of their genes in mouse islets and in the mouse β cell line MIN6. Peptides derived from the candidates were selected based on their predicted ability to bind H-2Kd and were examined for recognition by islet-infiltrating T cells from NOD mice. Several proteins, including those encoded by Abcc8, Atp2a2, Pcsk2, Peg3 and Scg2, were validated as antigens in this way. Interestingly, islet-infiltrating T cells were also found to recognize peptides derived from proglucagon, whose expression in pancreatic islets is associated with α cells, which are not usually implicated in type 1 diabetes pathogenesis. However, type 1 diabetes patients have been reported to have serum autoantibodies to glucagon, and NOD mouse studies have shown a decrease in α cell mass during disease pathogenesis. Our finding of islet-infiltrating glucagon-specific T cells is consistent with these reports and suggests the possibility of α cell involvement in development and progression of disease.

AB - Summary: Type 1 diabetes is characterized by T-cell-mediated destruction of the insulin-producing β cells in pancreatic islets. A number of islet antigens recognized by CD8 T cells that contribute to disease pathogenesis in non-obese diabetic (NOD) mice have been identified; however, the antigenic specificities of the majority of the islet-infiltrating cells have yet to be determined. The primary goal of the current study was to identify candidate antigens based on the level and specificity of expression of their genes in mouse islets and in the mouse β cell line MIN6. Peptides derived from the candidates were selected based on their predicted ability to bind H-2Kd and were examined for recognition by islet-infiltrating T cells from NOD mice. Several proteins, including those encoded by Abcc8, Atp2a2, Pcsk2, Peg3 and Scg2, were validated as antigens in this way. Interestingly, islet-infiltrating T cells were also found to recognize peptides derived from proglucagon, whose expression in pancreatic islets is associated with α cells, which are not usually implicated in type 1 diabetes pathogenesis. However, type 1 diabetes patients have been reported to have serum autoantibodies to glucagon, and NOD mouse studies have shown a decrease in α cell mass during disease pathogenesis. Our finding of islet-infiltrating glucagon-specific T cells is consistent with these reports and suggests the possibility of α cell involvement in development and progression of disease.

KW - Autoantigens

KW - Glucagon

KW - NOD mice

KW - Type 1 diabetes

UR - http://www.scopus.com/inward/record.url?scp=84924351936&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84924351936&partnerID=8YFLogxK

U2 - 10.1111/imm.12415

DO - 10.1111/imm.12415

M3 - Article

C2 - 25333865

AN - SCOPUS:84924351936

VL - 144

SP - 631

EP - 640

JO - Immunology

JF - Immunology

SN - 0019-2805

IS - 4

ER -