Abstract |
In the last decade, CD4+CD25+ T regulatory cells have been implicated in the protection against autoimmune diseases. The human DQ8 major histocompatibility complex ( MHC) class II molecule is associated with rheumatoid arthritis (RA) and various other autoimmune diseases in humans. The human leukocyte antigen (HLA)-DQ8 transgenic mouse, containing the human DQ8 MHC class II molecule, is predisposed toward collagen-induced arthritis. However, the biologic pathways responsible for DQ8-associated autoimmunity have yet to be defined, including possible defects in the CD4+CD25+ T regulatory cell compartment. To explore this concept, we examined the suppressive capacity of CD4+CD25+ T regulatory cells from DQ8 transgenic mice in vitro and, using CD25-specific depleting antibodies, investigated their influence on collagen-induced arthritis in vivo. CD4+CD25+ T regulatory cells isolated from DQ8 transgenic mice were found to be sufficient suppressors of splenocyte proliferation and interferon (INF)-gamma production. Furthermore, depletion of these cells before immunization led to significant increases in arthritis severity, collagen-specific antibodies, and INF-gamma production. These results indicate that HLA-DQ8 mice contain naturally occurring CD25+ regulatory cells that modulate collagen-induced arthritis and imply that DQ8 expression does not hinder the development of CD25+ T regulatory cells.
|
Authors | Mary E Morgan, Hendrik J Witteveen, Roger P M Sutmuller, René R P de Vries, René E M Toes |
Journal | Human immunology
(Hum Immunol)
Vol. 65
Issue 11
Pg. 1319-27
(Nov 2004)
ISSN: 0198-8859 [Print] United States |
PMID | 15556682
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Chemical References |
- Antibodies
- Collagen Type II
- HLA-DQ Antigens
- HLA-DQ8 antigen
- Receptors, Interleukin-2
- Interferon-gamma
|
Topics |
- Animals
- Antibodies
(blood, immunology)
- Arthritis, Experimental
(etiology, immunology)
- CD4-Positive T-Lymphocytes
(cytology, immunology)
- Collagen Type II
(immunology)
- HLA-DQ Antigens
(genetics, immunology)
- Humans
- Immune Tolerance
(immunology)
- Interferon-gamma
(metabolism)
- Lymphocyte Activation
(immunology)
- Lymphocyte Depletion
- Male
- Mice
- Mice, Inbred DBA
- Mice, Transgenic
- Receptors, Interleukin-2
(immunology)
- T-Lymphocytes
(metabolism)
|