Advanced

Self-reactive T cells induce and perpetuate chronic relapsing arthritis

Tuncel, Jonatan LU ; Holmberg, Jens LU ; Haag, Sabrina ; Hopkins, Malin Hultqvist LU ; Wester-Rosenlöf, Lena LU ; Carlsen, Stefan LU ; Olofsson, Peter LU and Holmdahl, Rikard LU (2020) In Arthritis Research and Therapy 22(1).
Abstract

Background: CD4+ T cells play a central role during the early stages of rheumatoid arthritis (RA), but to which extent they are required for the perpetuation of the disease is still not fully understood. The aim of the current study was to obtain conclusive evidence that T cells drive chronic relapsing arthritis. Methods: We used the rat pristane-induced arthritis model, which accurately portrays the chronic relapsing-remitting disease course of RA, to examine the contribution of T cells to chronic arthritis. Results: Rats subjected to whole-body irradiation and injected with CD4+ T cells from lymph nodes of pristane-injected donors developed chronic arthritis that lasted for more than 4 months, whereas T cells... (More)

Background: CD4+ T cells play a central role during the early stages of rheumatoid arthritis (RA), but to which extent they are required for the perpetuation of the disease is still not fully understood. The aim of the current study was to obtain conclusive evidence that T cells drive chronic relapsing arthritis. Methods: We used the rat pristane-induced arthritis model, which accurately portrays the chronic relapsing-remitting disease course of RA, to examine the contribution of T cells to chronic arthritis. Results: Rats subjected to whole-body irradiation and injected with CD4+ T cells from lymph nodes of pristane-injected donors developed chronic arthritis that lasted for more than 4 months, whereas T cells from the spleen only induced acute disease. Thymectomy in combination with irradiation enhanced the severity of arthritis, suggesting that sustained lymphopenia promotes T cell-driven chronic inflammation in this model. The ability of T cells to induce chronic arthritis correlated with their expression of Th17-associated transcripts, and while depletion of T cells in rats with chronic PIA led to transient, albeit significant, reduction in disease, neutralization of IL-17 resulted in almost complete and sustained remission. Conclusion: These findings show that, once activated, self-reactive T cells can sustain inflammatory responses for extended periods of time and suggest that such responses are promoted in the presence of IL-17.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Adoptive T cell transfer, Chronic arthritis, MHC class II, PIA, Pristane, RA, T cell depletion
in
Arthritis Research and Therapy
volume
22
issue
1
article number
95
publisher
BioMed Central (BMC)
external identifiers
  • scopus:85084107113
  • pmid:32345366
ISSN
1478-6354
DOI
10.1186/s13075-020-2104-7
language
English
LU publication?
yes
id
a4467ff5-b6a5-42c2-a936-48d15a3ed89e
date added to LUP
2020-05-20 08:17:03
date last changed
2020-05-21 03:00:10
@article{a4467ff5-b6a5-42c2-a936-48d15a3ed89e,
  abstract     = {<p>Background: CD4<sup>+</sup> T cells play a central role during the early stages of rheumatoid arthritis (RA), but to which extent they are required for the perpetuation of the disease is still not fully understood. The aim of the current study was to obtain conclusive evidence that T cells drive chronic relapsing arthritis. Methods: We used the rat pristane-induced arthritis model, which accurately portrays the chronic relapsing-remitting disease course of RA, to examine the contribution of T cells to chronic arthritis. Results: Rats subjected to whole-body irradiation and injected with CD4<sup>+</sup> T cells from lymph nodes of pristane-injected donors developed chronic arthritis that lasted for more than 4 months, whereas T cells from the spleen only induced acute disease. Thymectomy in combination with irradiation enhanced the severity of arthritis, suggesting that sustained lymphopenia promotes T cell-driven chronic inflammation in this model. The ability of T cells to induce chronic arthritis correlated with their expression of Th17-associated transcripts, and while depletion of T cells in rats with chronic PIA led to transient, albeit significant, reduction in disease, neutralization of IL-17 resulted in almost complete and sustained remission. Conclusion: These findings show that, once activated, self-reactive T cells can sustain inflammatory responses for extended periods of time and suggest that such responses are promoted in the presence of IL-17.</p>},
  author       = {Tuncel, Jonatan and Holmberg, Jens and Haag, Sabrina and Hopkins, Malin Hultqvist and Wester-Rosenlöf, Lena and Carlsen, Stefan and Olofsson, Peter and Holmdahl, Rikard},
  issn         = {1478-6354},
  language     = {eng},
  number       = {1},
  publisher    = {BioMed Central (BMC)},
  series       = {Arthritis Research and Therapy},
  title        = {Self-reactive T cells induce and perpetuate chronic relapsing arthritis},
  url          = {http://dx.doi.org/10.1186/s13075-020-2104-7},
  doi          = {10.1186/s13075-020-2104-7},
  volume       = {22},
  year         = {2020},
}