Regulatory T cells control epitope spreading in autoimmune arthritis independent of cytotoxic T-lymphocyte antigen-4 VOL EA, 1995, IMMUNITY, V3, P541

• CD4(+) Foxp3(+) regulatory T (Treg) cells can control both cellular and humoral immune responses; however, when and how Treg cells play a predominant role in regulating autoimmune disease remains elusive. To deplete Treg cells in vivo at given time-points, we used a mouse strain, susceptible to glucose-6-phosphate isomerase peptide-induced arthritis (GIA), in which the deletion of Treg cells can be controlled by diphtheria toxin treatment. By depleting Treg cells in the GIA mouse model, we found that a temporary lack of Treg cells at both priming and onset exaggerated disease development. Ablation of Treg cells led to the expansion of antigen-specific CD4(+) T cells including granulocyte-macrophage colony-stimulating factor, interferon-gamma and interleukin-17-producing T cells, and promoted both T-cell and B-cell epitope spreading, which perpetuated arthritis. Interestingly, specific depletion of cytotoxic T-lymphocyte antigen-4 (CTLA-4) on Treg cells only, was sufficient to protect mice from GIA, due to the expansion of CTLA-4(-) Treg cells expressing alternative suppressive molecules. Collectively, our findings suggest that Treg cells, independently of CTLA-4, act as the key driving force in controlling autoimmune arthritis development.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Immunology in the medical area (hsv//eng)

Nyckelord

autoimmune arthritis

cytotoxic T-lymphocyte antigen-4

epitope spreading

regulatory T cells

rheumatoid-arthritis

chronic inflammation

tissue attack

tnf-alpha

ctla-4

mice

disease

mechanisms

tolerance

adulthood

Immunology

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)