Vol.16 No.1

REVIEW ARTICLE

T-cell activation via CD26 and caveolin-1 in rheumatoid synovium

Authors

Kei Ohnuma1, Hiroshi Inoue2, Masahiko Uchiyama1, Tadanori Yamochi1, Osamu Hosono1, Nam H. Dang3 and Chikao Morimoto1

(1) Department of Clinical Immunology, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan
(2) Inoue Hospital, Takasaki, Japan
(3) Department of Hematologic Malignancies, Nevada Cancer Institute, Las Vegas, NV 89135, USA
Received:

13 September 2005

Accepted:

16 December 2005

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Abstract

CD26 is a T-cell costimulatory molecule with dipeptidyl peptidase IV (DPPIV) activity in its extracellular region. We previously reported that recombinant soluble CD26 enhances peripheral blood T-cell proliferation induced by the recall antigen tetanus toxoid (TT). Recently, we demonstrated that CD26 binds caveolin-1 on antigen-presenting cell (APC), and that residues 201-211 of CD26 along with the serine catalytic site at residue 630, which constitute a pocket structure of CD26/DPPIV, contribute to binding to caveolin-1 scaffolding domain. In addition, following CD26-caveolin-1 interaction on TT-loaded monocytes, caveolin-1 is phosphorylated, with linkage to NF-κB activation, followed by upregulation of CD86. Finally, reduced caveolin-1 expression on APC inhibits CD26-mediated CD86 upregulation and abrogates CD26 effect on TT-induced T-cell proliferation, and immunohistochemical studies revealed an infiltration of CD26+ T cells in the sublining region of rheumatoid synovium and high expression of caveolin-1 in the increased vasculature and synoviocytes of the rheumatoid synovium. Taken together, these results strongly suggest that CD26-cavolin-1 interaction plays a role in the upregulation of CD86 on TT-loaded APC and subsequent engagement with CD28 on T cells, leading to antigen-specific T-cell activation such as the T-cell-mediated antigen-specific response in rheumatoid arthritis.

Key words

Caveolin-1 - CD26 - Memory T cell - Rheumatoid arthritis (RA) - Synovial cell