In:
Signal Transduction, Wiley, Vol. 5, No. 5 ( 2005-10), p. 258-265
Abstract:
The ectoenzyme dipeptidyl peptidase IV (DP IV; E.C. 3.4.14.5; CD26) plays a crucial role in T cell activation, representing a new type of costimulatory T cell structure. Effectors of DP IV‐like activity, including naturally occurring and specific synthetic inhibitors, suppress DNA synthesis as well as cytokine production (IL‐2, IL‐10, IL‐12, IFN‐γ) of stimulated T cells. These effects are in part caused by the immunosuppressive cytokine TGF‐β1, leading to blockade of the cell cycle at the restriction point G1/S via p27 kip . At the same time, DP IV inhibitors provoke tyrosine phosphorylation and p38 MAP kinase activation.
Elevated numbers of CD26 + T cells were observed in patients with autoimmune diseases such as rheumatoid arthritis or multiple sclerosis (MS). The expression of DP IV/CD26 in resting T cell clones derived from patients with MS was found to be 3‐ to 4‐fold higher than on resting peripheral blood T cells from healthy persons. In myelin‐specific T cells from MS patients, DP IV inhibitors suppress DNA synthesis, as well as IFN‐γ, IL‐4 and TNF‐α production. Moreover, in experimental autoimmune encephalomyelitis (EAE), a well characterized CD4 + T cell‐mediated autoimmune disease leading to CNS inflammation and demyelinization, administration of a DP IV/CD26 inhibitor prevents clinical and neuropathological signs of EAE and suppresses ongoing disease.
This review summarizes evidence for the role of DP IV enzyme activity in regulation of T cell activation, outlines signal transduction mechanisms used or affected by this enzyme and provides support for the concept of a novel peptidase‐based immunosuppressive approach to treat autoimmune diseases like MS.
Type of Medium:
Online Resource
ISSN:
1615-4053
,
1615-4061
DOI:
10.1002/sita.200500069
Language:
English
Publisher:
Wiley
Publication Date:
2005
detail.hit.zdb_id:
2033020-0
SSG:
12
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