| Abstract | This paper reviews the existing evidence regarding the use of superagonistic anti-CD28 antibodies (CD28 superagonists) for therapeutic manipulation of regulatory T cells (T(reg) cells). The molecular properties of superagonistic anti-CD28 antibodies allow the generation of a strong activating signal in mature T cells, including T(reg) cells, without additional stimulation of the T cell receptor complex. CD28 superagonist administration in vivo leads to the preferential expansion and strong activation of naturally occurring CD4+CD25+CTLA-4+FoxP3+ T(reg) cells over conventional T cells. In animal models, both prophylactic and therapeutic administration of a CD28 superagonist prevented or at least greatly mitigated clinical symptoms and induced remission. Adoptive transfer experiments have further shown that CD28 superagonists mediate protection by expansion and activation of CD4+CD25+ T(reg) cells. Therefore, superagonistic anti-CD28 antibodies offer a promising novel treatment option for human autoimmune diseases and the first clinical trials are eagerly awaited. |
| Authors | N Beyersdorf, T Hanke, T Kerkau, T Hünig
(Affiliation: Institute for Virology and Immunobiology, University of Würzburg, Versbacherstr. 7, 97078 Würzburg, Germany.)
|
| Journal | Annals of the rheumatic diseases
(Ann Rheum Dis)
Vol. 64 Suppl 4
Pg. iv91-5
(Nov 2005)
ISSN: 0003-4967 England |
| PMID | 16239397
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
|
| Chemical References |
- Antibodies, Monoclonal
- Antigens, CD28
- Interleukin-2
|
| Topics |
- Animals
- Antibodies, Monoclonal
(immunology, therapeutic use)
- Antigens, CD28
(immunology)
- Autoimmune Diseases
(immunology, therapy)
- Humans
- Interleukin-2
(immunology)
- Lymphocyte Activation
(immunology)
- Rats
- T-Lymphocytes, Regulatory
(immunology)
|
