Prevention of spontaneous arthritis by inhibiting homeostatic expansion of autoreactive CD4+ T cells in the K/BxN mouse model
- Authors
- Jang, Eunkyeorig; Kim, Hong Ro; Cho, Sin Hye; Paik, Doo Jin; Kim, Jung Mogg; Lee, Sang-Koo; Youn, Jee hee
- Issue Date
- Feb-2006
- Publisher
- WILEY
- Citation
- ARTHRITIS AND RHEUMATISM, v.54, no.2, pp.492 - 498
- Indexed
- SCIE
SCOPUS
- Journal Title
- ARTHRITIS AND RHEUMATISM
- Volume
- 54
- Number
- 2
- Start Page
- 492
- End Page
- 498
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/181770
- DOI
- 10.1002/art.21567
- ISSN
- 0004-3591
- Abstract
- Objective. K/BxN-transgenic mice are a model of autoimmune arthritis, similar to rheumatoid arthritis. This study was undertaken to determine whether inhibition of lymphopenia-provoked homeostatic expansion can prevent spontaneous development of disease in the K/BxN model. Methods. To inhibit homeostatic expansion of autoreactive T cells, K/BxN mice with disease in the preclinical stage were adoptively transferred with CD4+ T cells purified from nontransgenic BxN or Thy1.1+ BxN mice. To observe the profile of proliferation of CD4+ T cells derived from the hosts, carboxyfluorescein diacetate succinimidyl ester-labeled autologous CD4+ T cells were cotransferred to K/BxN mice together with BxN CD4+ T cells. Disease onset and progression were scored, and the dynamics and phenotypes of recipient CD4+ T cells were determined by flow cytometry, before and after cell infusion. Results. During the preclinical phase of disease, K/BxN mice exhibited CD4+ T lymphopenia, which was followed by a compensatory expansion of these cells during the early clinical phase. The majority of CD4+ T cells acquired a memory phenotype (CD44(high) CD62L(low), CD25-), which is a hallmark of homeostatically expanding cells. Importantly, K/BxN mice subjected to syngeneic T cell transfer did not develop symptoms of arthritis and also possessed fewer transgenic T cell receptor-encoded V(beta)6+,CD4+ T cells. This effect was associated with decreased proliferation of recipient-derived CD4+ T cells but not with the function of CD25+ T regulatory cells present in donor cells. Conclusion. These results provide the first evidence that lymphopenia-associated homeostatic proliferation of autoreactive CD4+ T cells potentiates autoimmune arthritis, and that inhibition of this process protects mice from the development of this pathologic condition.
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