Nanoparticles containing an insulin-ChGA hybrid peptide protect from transfer of autoimmune diabetes by shifting the balance between effector T cells and regulatory T cells

Braxton L. Jamison, Tobias Neef, Andrew Goodspeed, Brenda Bradley, Rocky L. Baker, Stephen D Miller, Kathryn Haskins*

*Corresponding author for this work

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

CD4 T cells play a critical role in promoting the development of autoimmunity in type 1 diabetes. The diabetogenic CD4 T cell clone BDC-2.5, originally isolated from a NOD mouse, has been widely used to study the contribution of autoreactive CD4 T cells and relevant Ags to autoimmune diabetes. Recent work from our laboratory has shown that the Ag for BDC-2.5 T cells is a hybrid insulin peptide (2.5HIP) consisting of an insulin C-peptide fragment fused to a peptide from chromogranin A (ChgA) and that endogenous 2.5HIP-reactive T cells are major contributors to autoimmune pathology in NOD mice. The objective of this study was to determine if poly(lactide-co-glycolide) (PLG) nanoparticles (NPs) loaded with the 2.5HIP Ag (2.5HIP-coupled PLG NPs) can tolerize BDC-2.5 T cells. Infusion of 2.5HIP-coupled PLG NPs was found to prevent diabetes in an adoptive transfer model by impairing the ability of BDC-2.5 T cells to produce proinflammatory cytokines through induction of anergy, leading to an increase in the ratio of Foxp3+ regulatory T cells to IFN-g+ effector T cells. To our knowledge, this work is the first to use a hybrid insulin peptide, or any neoepitope, to re-educate diabetogenic T cells and may have significant implications for the development of an Ag-specific therapy for type 1 diabetes patients.

Original languageEnglish (US)
Pages (from-to)48-57
Number of pages10
JournalJournal of Immunology
Volume203
Issue number1
DOIs
StatePublished - Jan 1 2019

Fingerprint

Regulatory T-Lymphocytes
Type 1 Diabetes Mellitus
Nanoparticles
Insulin
T-Lymphocytes
Peptides
Inbred NOD Mouse
Polyglactin 910
Chromogranin A
Peptide Fragments
Adoptive Transfer
C-Peptide
Autoimmunity
Clone Cells
Pathology
Cytokines

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Jamison, Braxton L. ; Neef, Tobias ; Goodspeed, Andrew ; Bradley, Brenda ; Baker, Rocky L. ; Miller, Stephen D ; Haskins, Kathryn. / Nanoparticles containing an insulin-ChGA hybrid peptide protect from transfer of autoimmune diabetes by shifting the balance between effector T cells and regulatory T cells. In: Journal of Immunology. 2019 ; Vol. 203, No. 1. pp. 48-57.
@article{3b50fcba89e94a118fc7a0b0f8384eea,
title = "Nanoparticles containing an insulin-ChGA hybrid peptide protect from transfer of autoimmune diabetes by shifting the balance between effector T cells and regulatory T cells",
abstract = "CD4 T cells play a critical role in promoting the development of autoimmunity in type 1 diabetes. The diabetogenic CD4 T cell clone BDC-2.5, originally isolated from a NOD mouse, has been widely used to study the contribution of autoreactive CD4 T cells and relevant Ags to autoimmune diabetes. Recent work from our laboratory has shown that the Ag for BDC-2.5 T cells is a hybrid insulin peptide (2.5HIP) consisting of an insulin C-peptide fragment fused to a peptide from chromogranin A (ChgA) and that endogenous 2.5HIP-reactive T cells are major contributors to autoimmune pathology in NOD mice. The objective of this study was to determine if poly(lactide-co-glycolide) (PLG) nanoparticles (NPs) loaded with the 2.5HIP Ag (2.5HIP-coupled PLG NPs) can tolerize BDC-2.5 T cells. Infusion of 2.5HIP-coupled PLG NPs was found to prevent diabetes in an adoptive transfer model by impairing the ability of BDC-2.5 T cells to produce proinflammatory cytokines through induction of anergy, leading to an increase in the ratio of Foxp3+ regulatory T cells to IFN-g+ effector T cells. To our knowledge, this work is the first to use a hybrid insulin peptide, or any neoepitope, to re-educate diabetogenic T cells and may have significant implications for the development of an Ag-specific therapy for type 1 diabetes patients.",
author = "Jamison, {Braxton L.} and Tobias Neef and Andrew Goodspeed and Brenda Bradley and Baker, {Rocky L.} and Miller, {Stephen D} and Kathryn Haskins",
year = "2019",
month = "1",
day = "1",
doi = "10.4049/jimmunol.1900127",
language = "English (US)",
volume = "203",
pages = "48--57",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "1",

}

Nanoparticles containing an insulin-ChGA hybrid peptide protect from transfer of autoimmune diabetes by shifting the balance between effector T cells and regulatory T cells. / Jamison, Braxton L.; Neef, Tobias; Goodspeed, Andrew; Bradley, Brenda; Baker, Rocky L.; Miller, Stephen D; Haskins, Kathryn.

In: Journal of Immunology, Vol. 203, No. 1, 01.01.2019, p. 48-57.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Nanoparticles containing an insulin-ChGA hybrid peptide protect from transfer of autoimmune diabetes by shifting the balance between effector T cells and regulatory T cells

AU - Jamison, Braxton L.

AU - Neef, Tobias

AU - Goodspeed, Andrew

AU - Bradley, Brenda

AU - Baker, Rocky L.

AU - Miller, Stephen D

AU - Haskins, Kathryn

PY - 2019/1/1

Y1 - 2019/1/1

N2 - CD4 T cells play a critical role in promoting the development of autoimmunity in type 1 diabetes. The diabetogenic CD4 T cell clone BDC-2.5, originally isolated from a NOD mouse, has been widely used to study the contribution of autoreactive CD4 T cells and relevant Ags to autoimmune diabetes. Recent work from our laboratory has shown that the Ag for BDC-2.5 T cells is a hybrid insulin peptide (2.5HIP) consisting of an insulin C-peptide fragment fused to a peptide from chromogranin A (ChgA) and that endogenous 2.5HIP-reactive T cells are major contributors to autoimmune pathology in NOD mice. The objective of this study was to determine if poly(lactide-co-glycolide) (PLG) nanoparticles (NPs) loaded with the 2.5HIP Ag (2.5HIP-coupled PLG NPs) can tolerize BDC-2.5 T cells. Infusion of 2.5HIP-coupled PLG NPs was found to prevent diabetes in an adoptive transfer model by impairing the ability of BDC-2.5 T cells to produce proinflammatory cytokines through induction of anergy, leading to an increase in the ratio of Foxp3+ regulatory T cells to IFN-g+ effector T cells. To our knowledge, this work is the first to use a hybrid insulin peptide, or any neoepitope, to re-educate diabetogenic T cells and may have significant implications for the development of an Ag-specific therapy for type 1 diabetes patients.

AB - CD4 T cells play a critical role in promoting the development of autoimmunity in type 1 diabetes. The diabetogenic CD4 T cell clone BDC-2.5, originally isolated from a NOD mouse, has been widely used to study the contribution of autoreactive CD4 T cells and relevant Ags to autoimmune diabetes. Recent work from our laboratory has shown that the Ag for BDC-2.5 T cells is a hybrid insulin peptide (2.5HIP) consisting of an insulin C-peptide fragment fused to a peptide from chromogranin A (ChgA) and that endogenous 2.5HIP-reactive T cells are major contributors to autoimmune pathology in NOD mice. The objective of this study was to determine if poly(lactide-co-glycolide) (PLG) nanoparticles (NPs) loaded with the 2.5HIP Ag (2.5HIP-coupled PLG NPs) can tolerize BDC-2.5 T cells. Infusion of 2.5HIP-coupled PLG NPs was found to prevent diabetes in an adoptive transfer model by impairing the ability of BDC-2.5 T cells to produce proinflammatory cytokines through induction of anergy, leading to an increase in the ratio of Foxp3+ regulatory T cells to IFN-g+ effector T cells. To our knowledge, this work is the first to use a hybrid insulin peptide, or any neoepitope, to re-educate diabetogenic T cells and may have significant implications for the development of an Ag-specific therapy for type 1 diabetes patients.

UR - http://www.scopus.com/inward/record.url?scp=85068429779&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85068429779&partnerID=8YFLogxK

U2 - 10.4049/jimmunol.1900127

DO - 10.4049/jimmunol.1900127

M3 - Article

C2 - 31109955

AN - SCOPUS:85068429779

VL - 203

SP - 48

EP - 57

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 1

ER -