CD8 T-cell reactivity to islet antigens is unique to type 1 while CD4 T-cell reactivity exists in both type 1 and type 2 diabetes

Ghanashyam Sarikonda, Jeremy Pettus, Sonal Phatak, Sowbarnika Sachithanantham, Jacqueline F. Miller, Johnna D. Wesley, Eithon Cadag, Ji Chae, Lakshmi Ganesan, Ronna Mallios, Steve Edelman, Bjoern Peters, Matthias Von Herrath

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

Previous cross-sectional analyses demonstrated that CD8+ and CD4+ T-cell reactivity to islet-specific antigens was more prevalent in T1D subjects than in healthy donors (HD). Here, we examined T1D-associated epitope-specific CD4+ T-cell cytokine production and autoreactive CD8+ T-cell frequency on a monthly basis for one year in 10 HD, 33 subjects with T1D, and 15 subjects with T2D. Autoreactive CD4+ T-cells from both T1D and T2D subjects produced more IFN-γ when stimulated than cells from HD. In contrast, higher frequencies of islet antigen-specific CD8+ T-cells were detected only in T1D. These observations support the hypothesis that general beta-cell stress drives autoreactive CD4+ T-cell activity while islet over-expression of MHC class I commonly seen in T1D mediates amplification of CD8+ T-cells and more rapid beta-cell loss. In conclusion, CD4+ T-cell autoreactivity appears to be present in both T1D and T2D while autoreactive CD8+ T-cells are unique to T1D. Thus, autoreactive CD8+ cells may serve as a more T1D-specific biomarker.

Original languageEnglish (US)
Pages (from-to)77-82
Number of pages6
JournalJournal of Autoimmunity
Volume50
DOIs
StatePublished - 2014

Fingerprint

Type 1 Diabetes Mellitus
Type 2 Diabetes Mellitus
T-Lymphocytes
Antigens
Tissue Donors
CD8 Antigens
Epitopes
Healthy Volunteers
Cross-Sectional Studies
Biomarkers
Cytokines

Keywords

  • Antigen specific T-cells
  • ELISpot
  • HLA-Qdot-multimer analysis
  • Type 1 diabetes

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Medicine(all)

Cite this

CD8 T-cell reactivity to islet antigens is unique to type 1 while CD4 T-cell reactivity exists in both type 1 and type 2 diabetes. / Sarikonda, Ghanashyam; Pettus, Jeremy; Phatak, Sonal; Sachithanantham, Sowbarnika; Miller, Jacqueline F.; Wesley, Johnna D.; Cadag, Eithon; Chae, Ji; Ganesan, Lakshmi; Mallios, Ronna; Edelman, Steve; Peters, Bjoern; Von Herrath, Matthias.

In: Journal of Autoimmunity, Vol. 50, 2014, p. 77-82.

Research output: Contribution to journalArticle

Sarikonda, G, Pettus, J, Phatak, S, Sachithanantham, S, Miller, JF, Wesley, JD, Cadag, E, Chae, J, Ganesan, L, Mallios, R, Edelman, S, Peters, B & Von Herrath, M 2014, 'CD8 T-cell reactivity to islet antigens is unique to type 1 while CD4 T-cell reactivity exists in both type 1 and type 2 diabetes', Journal of Autoimmunity, vol. 50, pp. 77-82. https://doi.org/10.1016/j.jaut.2013.12.003
Sarikonda, Ghanashyam ; Pettus, Jeremy ; Phatak, Sonal ; Sachithanantham, Sowbarnika ; Miller, Jacqueline F. ; Wesley, Johnna D. ; Cadag, Eithon ; Chae, Ji ; Ganesan, Lakshmi ; Mallios, Ronna ; Edelman, Steve ; Peters, Bjoern ; Von Herrath, Matthias. / CD8 T-cell reactivity to islet antigens is unique to type 1 while CD4 T-cell reactivity exists in both type 1 and type 2 diabetes. In: Journal of Autoimmunity. 2014 ; Vol. 50. pp. 77-82.
@article{95bf100dc39a46458a296cb807fa95b5,
title = "CD8 T-cell reactivity to islet antigens is unique to type 1 while CD4 T-cell reactivity exists in both type 1 and type 2 diabetes",
abstract = "Previous cross-sectional analyses demonstrated that CD8+ and CD4+ T-cell reactivity to islet-specific antigens was more prevalent in T1D subjects than in healthy donors (HD). Here, we examined T1D-associated epitope-specific CD4+ T-cell cytokine production and autoreactive CD8+ T-cell frequency on a monthly basis for one year in 10 HD, 33 subjects with T1D, and 15 subjects with T2D. Autoreactive CD4+ T-cells from both T1D and T2D subjects produced more IFN-γ when stimulated than cells from HD. In contrast, higher frequencies of islet antigen-specific CD8+ T-cells were detected only in T1D. These observations support the hypothesis that general beta-cell stress drives autoreactive CD4+ T-cell activity while islet over-expression of MHC class I commonly seen in T1D mediates amplification of CD8+ T-cells and more rapid beta-cell loss. In conclusion, CD4+ T-cell autoreactivity appears to be present in both T1D and T2D while autoreactive CD8+ T-cells are unique to T1D. Thus, autoreactive CD8+ cells may serve as a more T1D-specific biomarker.",
keywords = "Antigen specific T-cells, ELISpot, HLA-Qdot-multimer analysis, Type 1 diabetes",
author = "Ghanashyam Sarikonda and Jeremy Pettus and Sonal Phatak and Sowbarnika Sachithanantham and Miller, {Jacqueline F.} and Wesley, {Johnna D.} and Eithon Cadag and Ji Chae and Lakshmi Ganesan and Ronna Mallios and Steve Edelman and Bjoern Peters and {Von Herrath}, Matthias",
year = "2014",
doi = "10.1016/j.jaut.2013.12.003",
language = "English (US)",
volume = "50",
pages = "77--82",
journal = "Journal of Autoimmunity",
issn = "0896-8411",
publisher = "Academic Press Inc.",

}

TY - JOUR

T1 - CD8 T-cell reactivity to islet antigens is unique to type 1 while CD4 T-cell reactivity exists in both type 1 and type 2 diabetes

AU - Sarikonda, Ghanashyam

AU - Pettus, Jeremy

AU - Phatak, Sonal

AU - Sachithanantham, Sowbarnika

AU - Miller, Jacqueline F.

AU - Wesley, Johnna D.

AU - Cadag, Eithon

AU - Chae, Ji

AU - Ganesan, Lakshmi

AU - Mallios, Ronna

AU - Edelman, Steve

AU - Peters, Bjoern

AU - Von Herrath, Matthias

PY - 2014

Y1 - 2014

N2 - Previous cross-sectional analyses demonstrated that CD8+ and CD4+ T-cell reactivity to islet-specific antigens was more prevalent in T1D subjects than in healthy donors (HD). Here, we examined T1D-associated epitope-specific CD4+ T-cell cytokine production and autoreactive CD8+ T-cell frequency on a monthly basis for one year in 10 HD, 33 subjects with T1D, and 15 subjects with T2D. Autoreactive CD4+ T-cells from both T1D and T2D subjects produced more IFN-γ when stimulated than cells from HD. In contrast, higher frequencies of islet antigen-specific CD8+ T-cells were detected only in T1D. These observations support the hypothesis that general beta-cell stress drives autoreactive CD4+ T-cell activity while islet over-expression of MHC class I commonly seen in T1D mediates amplification of CD8+ T-cells and more rapid beta-cell loss. In conclusion, CD4+ T-cell autoreactivity appears to be present in both T1D and T2D while autoreactive CD8+ T-cells are unique to T1D. Thus, autoreactive CD8+ cells may serve as a more T1D-specific biomarker.

AB - Previous cross-sectional analyses demonstrated that CD8+ and CD4+ T-cell reactivity to islet-specific antigens was more prevalent in T1D subjects than in healthy donors (HD). Here, we examined T1D-associated epitope-specific CD4+ T-cell cytokine production and autoreactive CD8+ T-cell frequency on a monthly basis for one year in 10 HD, 33 subjects with T1D, and 15 subjects with T2D. Autoreactive CD4+ T-cells from both T1D and T2D subjects produced more IFN-γ when stimulated than cells from HD. In contrast, higher frequencies of islet antigen-specific CD8+ T-cells were detected only in T1D. These observations support the hypothesis that general beta-cell stress drives autoreactive CD4+ T-cell activity while islet over-expression of MHC class I commonly seen in T1D mediates amplification of CD8+ T-cells and more rapid beta-cell loss. In conclusion, CD4+ T-cell autoreactivity appears to be present in both T1D and T2D while autoreactive CD8+ T-cells are unique to T1D. Thus, autoreactive CD8+ cells may serve as a more T1D-specific biomarker.

KW - Antigen specific T-cells

KW - ELISpot

KW - HLA-Qdot-multimer analysis

KW - Type 1 diabetes

UR - http://www.scopus.com/inward/record.url?scp=84899074071&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84899074071&partnerID=8YFLogxK

U2 - 10.1016/j.jaut.2013.12.003

DO - 10.1016/j.jaut.2013.12.003

M3 - Article

VL - 50

SP - 77

EP - 82

JO - Journal of Autoimmunity

JF - Journal of Autoimmunity

SN - 0896-8411

ER -