Simultaneous recognition of allogeneic MHC and cognate autoantigen by autoreactive t cells in transplant rejection

Adam L. Burrack, Laurie G. Landry, Janet Siebert, Marilyne Coulombe, Ronald G. Gill, Maki Nakayama

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

The autoimmune condition is a primary obstacle to inducing tolerance in type 1 diabetes patients receiving allogeneic pancreas transplants. It is unknown how autoreactive T cells that recognize self-MHC molecules contribute to MHC-disparate allograft rejection. In this report, we show the presence and accumulation of dual-reactive, that is autoreactive and alloreactive, T cells in C3H islet allografts that were transplanted into autoimmune diabetic NOD mice. Using high-throughput sequencing, we discovered that T cells prevalent in allografts share identical TCRs with autoreactive T cells present in pancreatic islets. T cells expressing TCRs that are enriched in allograft lesions recognized C3H MHC molecules, and five of six cell lines expressing these TCRs were also reactive to NOD islet cells. These results reveal the presence of autoreactive T cells that mediate cross-reactive alloreactivity, and indicate a requirement for regulating such dual-reactive T cells in tissue replacement therapies given to autoimmune individuals. The Journal of Immunology, 2018, 200: 1504–1512.

Original languageEnglish (US)
Pages (from-to)1504-1512
Number of pages9
JournalJournal of Immunology
Volume200
Issue number4
DOIs
StatePublished - Feb 15 2018

Fingerprint

Autoantigens
Graft Rejection
T-Lymphocytes
Transplants
Allografts
Islets of Langerhans
Inbred NOD Mouse
Cell- and Tissue-Based Therapy
Allergy and Immunology
Type 1 Diabetes Mellitus
Pancreas
Cell Line

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

Cite this

Simultaneous recognition of allogeneic MHC and cognate autoantigen by autoreactive t cells in transplant rejection. / Burrack, Adam L.; Landry, Laurie G.; Siebert, Janet; Coulombe, Marilyne; Gill, Ronald G.; Nakayama, Maki.

In: Journal of Immunology, Vol. 200, No. 4, 15.02.2018, p. 1504-1512.

Research output: Contribution to journalArticle

Burrack, Adam L. ; Landry, Laurie G. ; Siebert, Janet ; Coulombe, Marilyne ; Gill, Ronald G. ; Nakayama, Maki. / Simultaneous recognition of allogeneic MHC and cognate autoantigen by autoreactive t cells in transplant rejection. In: Journal of Immunology. 2018 ; Vol. 200, No. 4. pp. 1504-1512.
@article{7cda1d97671545428e3fbb8e339db172,
title = "Simultaneous recognition of allogeneic MHC and cognate autoantigen by autoreactive t cells in transplant rejection",
abstract = "The autoimmune condition is a primary obstacle to inducing tolerance in type 1 diabetes patients receiving allogeneic pancreas transplants. It is unknown how autoreactive T cells that recognize self-MHC molecules contribute to MHC-disparate allograft rejection. In this report, we show the presence and accumulation of dual-reactive, that is autoreactive and alloreactive, T cells in C3H islet allografts that were transplanted into autoimmune diabetic NOD mice. Using high-throughput sequencing, we discovered that T cells prevalent in allografts share identical TCRs with autoreactive T cells present in pancreatic islets. T cells expressing TCRs that are enriched in allograft lesions recognized C3H MHC molecules, and five of six cell lines expressing these TCRs were also reactive to NOD islet cells. These results reveal the presence of autoreactive T cells that mediate cross-reactive alloreactivity, and indicate a requirement for regulating such dual-reactive T cells in tissue replacement therapies given to autoimmune individuals. The Journal of Immunology, 2018, 200: 1504–1512.",
author = "Burrack, {Adam L.} and Landry, {Laurie G.} and Janet Siebert and Marilyne Coulombe and Gill, {Ronald G.} and Maki Nakayama",
year = "2018",
month = "2",
day = "15",
doi = "10.4049/jimmunol.1700856",
language = "English (US)",
volume = "200",
pages = "1504--1512",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "4",

}

TY - JOUR

T1 - Simultaneous recognition of allogeneic MHC and cognate autoantigen by autoreactive t cells in transplant rejection

AU - Burrack, Adam L.

AU - Landry, Laurie G.

AU - Siebert, Janet

AU - Coulombe, Marilyne

AU - Gill, Ronald G.

AU - Nakayama, Maki

PY - 2018/2/15

Y1 - 2018/2/15

N2 - The autoimmune condition is a primary obstacle to inducing tolerance in type 1 diabetes patients receiving allogeneic pancreas transplants. It is unknown how autoreactive T cells that recognize self-MHC molecules contribute to MHC-disparate allograft rejection. In this report, we show the presence and accumulation of dual-reactive, that is autoreactive and alloreactive, T cells in C3H islet allografts that were transplanted into autoimmune diabetic NOD mice. Using high-throughput sequencing, we discovered that T cells prevalent in allografts share identical TCRs with autoreactive T cells present in pancreatic islets. T cells expressing TCRs that are enriched in allograft lesions recognized C3H MHC molecules, and five of six cell lines expressing these TCRs were also reactive to NOD islet cells. These results reveal the presence of autoreactive T cells that mediate cross-reactive alloreactivity, and indicate a requirement for regulating such dual-reactive T cells in tissue replacement therapies given to autoimmune individuals. The Journal of Immunology, 2018, 200: 1504–1512.

AB - The autoimmune condition is a primary obstacle to inducing tolerance in type 1 diabetes patients receiving allogeneic pancreas transplants. It is unknown how autoreactive T cells that recognize self-MHC molecules contribute to MHC-disparate allograft rejection. In this report, we show the presence and accumulation of dual-reactive, that is autoreactive and alloreactive, T cells in C3H islet allografts that were transplanted into autoimmune diabetic NOD mice. Using high-throughput sequencing, we discovered that T cells prevalent in allografts share identical TCRs with autoreactive T cells present in pancreatic islets. T cells expressing TCRs that are enriched in allograft lesions recognized C3H MHC molecules, and five of six cell lines expressing these TCRs were also reactive to NOD islet cells. These results reveal the presence of autoreactive T cells that mediate cross-reactive alloreactivity, and indicate a requirement for regulating such dual-reactive T cells in tissue replacement therapies given to autoimmune individuals. The Journal of Immunology, 2018, 200: 1504–1512.

UR - http://www.scopus.com/inward/record.url?scp=85044724523&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85044724523&partnerID=8YFLogxK

U2 - 10.4049/jimmunol.1700856

DO - 10.4049/jimmunol.1700856

M3 - Article

C2 - 29311365

AN - SCOPUS:85044724523

VL - 200

SP - 1504

EP - 1512

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 4

ER -