| Abstract | Autoreactive T cells are thought to be involved in the pathogenesis of autoimmune diseases, but evidence for their direct pathogenicity is almost lacking. Herein we established a unique system for evaluating the in vivo pathogenicity of desmoglein 3 (Dsg3)-reactive T cells at a clonal level in a mouse model for pemphigus vulgaris (PV), an autoimmune blistering disease induced by anti-Dsg3 autoantibodies. Dsg3-reactive CD4(+) T cell lines generated in vitro were adoptively transferred into Rag-2(-/-) mice with primed B cells derived from Dsg3-immunized Dsg3(-/-) mice. Seven of 20 T cell lines induced IgG anti-Dsg3 Ab production and acantholytic blister, a typical disease phenotype, in recipient mice. Comparison of the characteristics between pathogenic and nonpathogenic Dsg3-reactive T cell lines led to the identification of IL-4 and IL-10 as potential factors associated with pathogenicity. Further in vitro analysis showed that IL-4, but not IL-10, promoted IgG anti-Dsg3 Ab production by primed B cells. Additionally, adenoviral expression of soluble IL-4Ralpha in vivo suppressed IgG anti-Dsg3 Ab production and the PV phenotype, indicating a pathogenic role of IL-4. This strategy is useful for evaluating the effector function of autoreactive T cells involved in the pathogenesis of various autoimmune diseases. |
| Authors | Hayato Takahashi, Masayuki Amagai, Takeji Nishikawa, Yoshiko Fujii, Yutaka Kawakami, Masataka Kuwana
(Affiliation: Department of Dermatology, Keio University School of Medicine, Tokyo, Japan.)
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| Journal | Journal of immunology (Baltimore, Md. : 1950)
(J Immunol)
Vol. 181
Issue 2
Pg. 1526-35
(Jul 15 2008)
ISSN: 1550-6606 United States |
| PMID | 18606708
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
| Chemical References |
- Autoantibodies
- Desmoglein 3
- Il4ra protein, mouse
- Receptors, Cell Surface
- Recombinant Proteins
- Interleukin-10
- Interleukin-4
- Interferon-gamma
|
| Topics |
- Adoptive Transfer
- Animals
- Autoantibodies
(immunology)
- B-Lymphocytes
(immunology)
- CD4-Positive T-Lymphocytes
(immunology, metabolism)
- Cell Line
- Desmoglein 3
(immunology)
- Interferon-gamma
(immunology, metabolism)
- Interleukin-10
(immunology, physiology)
- Interleukin-4
(immunology, physiology)
- Mice
- Mice, Knockout
- Pemphigus
(immunology)
- Receptors, Cell Surface
(metabolism)
- Recombinant Proteins
(metabolism)
- T-Lymphocytes
(cytology, immunology, metabolism)
|
