αB-Crystallin-reactive T cells from knockout mice are not encephalitogenic

Chunhe Wang, Yuan K. Chou, Cathleen M. Rich, Jason Link, Michael E. Afentoulis, Johannes M. van Noort, Eric F. Wawrousek, Halina Offner, Arthur Vandenbark

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Alpha B-crystallin (αB) is a small heat shock protein that is strongly up-regulated in multiple sclerosis (MS) brain tissue, and can induce strong T cell responses. Assessing a potential encephalitogenic function for αB protein in MS and experimental autoimmune encephalomyelitis (EAE) has been challenging due to its ubiquitous expression that likely maintains central and peripheral tolerance to this protein in mice. To address this issue, we obtained αB-knockout (αB-KO) mice in H-2b background that lack immune tolerance to αB protein, and thus are capable of developing αB-specific T cells that could be tested for encephalitogenic activity after transfer into αB-expressing wild type (WT) mice. We found that T cell lines from spleens of αB protein-immunized αB-KO mice proliferated strongly to αB protein itself, and the majority of T cells were CD4+ and capable of secreting pro-inflammatory Th1 cytokines upon restimulation. However, transfer of such αB-reactive T cells back into WT recipients was not sufficient to induce EAE, compared to the transfer of mouse MOG-35-55 peptide-reactive T cells from the same donors that induced severe EAE in recipients. Moreover, αB-specific T cells failed to augment severity of actively induced EAE in WT mice that were expressing high levels of αB message in the CNS at the time of transfer. These results suggest that αB-specific T cells are immunocompetent but not encephalitogenic in 129SvEv mice, and that immune tolerance may not be the main factor that limits the encephalitogenic potential of αB.

Original languageEnglish (US)
Pages (from-to)51-62
Number of pages12
JournalJournal of Neuroimmunology
Volume176
Issue number1-2
DOIs
StatePublished - Jul 2006

Fingerprint

Crystallins
Knockout Mice
T-Lymphocytes
Autoimmune Experimental Encephalomyelitis
Immune Tolerance
Multiple Sclerosis
alpha-Crystallin B Chain
Central Tolerance
Small Heat-Shock Proteins
Peripheral Tolerance
Peptide T
Spleen
Cytokines
Cell Line
IgA receptor
Brain

Keywords

  • EAE/MS
  • Knockout mice
  • T cells
  • Tolerance

ASJC Scopus subject areas

  • Immunology
  • Clinical Neurology
  • Immunology and Allergy
  • Neurology

Cite this

αB-Crystallin-reactive T cells from knockout mice are not encephalitogenic. / Wang, Chunhe; Chou, Yuan K.; Rich, Cathleen M.; Link, Jason; Afentoulis, Michael E.; van Noort, Johannes M.; Wawrousek, Eric F.; Offner, Halina; Vandenbark, Arthur.

In: Journal of Neuroimmunology, Vol. 176, No. 1-2, 07.2006, p. 51-62.

Research output: Contribution to journalArticle

Wang, Chunhe ; Chou, Yuan K. ; Rich, Cathleen M. ; Link, Jason ; Afentoulis, Michael E. ; van Noort, Johannes M. ; Wawrousek, Eric F. ; Offner, Halina ; Vandenbark, Arthur. / αB-Crystallin-reactive T cells from knockout mice are not encephalitogenic. In: Journal of Neuroimmunology. 2006 ; Vol. 176, No. 1-2. pp. 51-62.
@article{6ccaece5cd304aceb6e0d5ae66e10ffc,
title = "αB-Crystallin-reactive T cells from knockout mice are not encephalitogenic",
abstract = "Alpha B-crystallin (αB) is a small heat shock protein that is strongly up-regulated in multiple sclerosis (MS) brain tissue, and can induce strong T cell responses. Assessing a potential encephalitogenic function for αB protein in MS and experimental autoimmune encephalomyelitis (EAE) has been challenging due to its ubiquitous expression that likely maintains central and peripheral tolerance to this protein in mice. To address this issue, we obtained αB-knockout (αB-KO) mice in H-2b background that lack immune tolerance to αB protein, and thus are capable of developing αB-specific T cells that could be tested for encephalitogenic activity after transfer into αB-expressing wild type (WT) mice. We found that T cell lines from spleens of αB protein-immunized αB-KO mice proliferated strongly to αB protein itself, and the majority of T cells were CD4+ and capable of secreting pro-inflammatory Th1 cytokines upon restimulation. However, transfer of such αB-reactive T cells back into WT recipients was not sufficient to induce EAE, compared to the transfer of mouse MOG-35-55 peptide-reactive T cells from the same donors that induced severe EAE in recipients. Moreover, αB-specific T cells failed to augment severity of actively induced EAE in WT mice that were expressing high levels of αB message in the CNS at the time of transfer. These results suggest that αB-specific T cells are immunocompetent but not encephalitogenic in 129SvEv mice, and that immune tolerance may not be the main factor that limits the encephalitogenic potential of αB.",
keywords = "EAE/MS, Knockout mice, T cells, Tolerance",
author = "Chunhe Wang and Chou, {Yuan K.} and Rich, {Cathleen M.} and Jason Link and Afentoulis, {Michael E.} and {van Noort}, {Johannes M.} and Wawrousek, {Eric F.} and Halina Offner and Arthur Vandenbark",
year = "2006",
month = "7",
doi = "10.1016/j.jneuroim.2006.04.010",
language = "English (US)",
volume = "176",
pages = "51--62",
journal = "Journal of Neuroimmunology",
issn = "0165-5728",
publisher = "Elsevier",
number = "1-2",

}

TY - JOUR

T1 - αB-Crystallin-reactive T cells from knockout mice are not encephalitogenic

AU - Wang, Chunhe

AU - Chou, Yuan K.

AU - Rich, Cathleen M.

AU - Link, Jason

AU - Afentoulis, Michael E.

AU - van Noort, Johannes M.

AU - Wawrousek, Eric F.

AU - Offner, Halina

AU - Vandenbark, Arthur

PY - 2006/7

Y1 - 2006/7

N2 - Alpha B-crystallin (αB) is a small heat shock protein that is strongly up-regulated in multiple sclerosis (MS) brain tissue, and can induce strong T cell responses. Assessing a potential encephalitogenic function for αB protein in MS and experimental autoimmune encephalomyelitis (EAE) has been challenging due to its ubiquitous expression that likely maintains central and peripheral tolerance to this protein in mice. To address this issue, we obtained αB-knockout (αB-KO) mice in H-2b background that lack immune tolerance to αB protein, and thus are capable of developing αB-specific T cells that could be tested for encephalitogenic activity after transfer into αB-expressing wild type (WT) mice. We found that T cell lines from spleens of αB protein-immunized αB-KO mice proliferated strongly to αB protein itself, and the majority of T cells were CD4+ and capable of secreting pro-inflammatory Th1 cytokines upon restimulation. However, transfer of such αB-reactive T cells back into WT recipients was not sufficient to induce EAE, compared to the transfer of mouse MOG-35-55 peptide-reactive T cells from the same donors that induced severe EAE in recipients. Moreover, αB-specific T cells failed to augment severity of actively induced EAE in WT mice that were expressing high levels of αB message in the CNS at the time of transfer. These results suggest that αB-specific T cells are immunocompetent but not encephalitogenic in 129SvEv mice, and that immune tolerance may not be the main factor that limits the encephalitogenic potential of αB.

AB - Alpha B-crystallin (αB) is a small heat shock protein that is strongly up-regulated in multiple sclerosis (MS) brain tissue, and can induce strong T cell responses. Assessing a potential encephalitogenic function for αB protein in MS and experimental autoimmune encephalomyelitis (EAE) has been challenging due to its ubiquitous expression that likely maintains central and peripheral tolerance to this protein in mice. To address this issue, we obtained αB-knockout (αB-KO) mice in H-2b background that lack immune tolerance to αB protein, and thus are capable of developing αB-specific T cells that could be tested for encephalitogenic activity after transfer into αB-expressing wild type (WT) mice. We found that T cell lines from spleens of αB protein-immunized αB-KO mice proliferated strongly to αB protein itself, and the majority of T cells were CD4+ and capable of secreting pro-inflammatory Th1 cytokines upon restimulation. However, transfer of such αB-reactive T cells back into WT recipients was not sufficient to induce EAE, compared to the transfer of mouse MOG-35-55 peptide-reactive T cells from the same donors that induced severe EAE in recipients. Moreover, αB-specific T cells failed to augment severity of actively induced EAE in WT mice that were expressing high levels of αB message in the CNS at the time of transfer. These results suggest that αB-specific T cells are immunocompetent but not encephalitogenic in 129SvEv mice, and that immune tolerance may not be the main factor that limits the encephalitogenic potential of αB.

KW - EAE/MS

KW - Knockout mice

KW - T cells

KW - Tolerance

UR - http://www.scopus.com/inward/record.url?scp=33746040093&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33746040093&partnerID=8YFLogxK

U2 - 10.1016/j.jneuroim.2006.04.010

DO - 10.1016/j.jneuroim.2006.04.010

M3 - Article

C2 - 16844233

AN - SCOPUS:33746040093

VL - 176

SP - 51

EP - 62

JO - Journal of Neuroimmunology

JF - Journal of Neuroimmunology

SN - 0165-5728

IS - 1-2

ER -