In rheumatoid arthritis soluble CD30 ligand is present at high levels and induces apoptosis of CD30(+)T cells.
CD30 and CD30 ligand (CD30L) are members of TNF-receptor and TNF superfamilies respectively. CD30(+)T cells are increased in several diseases and interaction between CD30(+) and CD30L(+)T cells leads either to cell proliferation or apoptosis. In patients with rheumatoid arthritis (RA), soluble CD30 (sCD30) levels seem to reflect the recruitment of CD30(+)T cells into the inflamed joints and are predictive of a positive response to classical and biological immunosuppressive therapy. We have evaluated the presence of soluble CD30L (sCD30L) in the sera and synovial fluid of patients with RA and defined whether it binds surface CD30 molecule and is functionally active. We found high levels of sCD30L in sera and synovial fluid of RA patients; the molecule is shedded upon direct contact of CD30(+)/CD30L(+)T cells. Moreover sCD30L binds surface CD30 constitutively expressed by Jurkat cell line. Finally recombinant sCD30L and sera from patients with high levels of sCD30L are able to inhibit CD30(+)T cell proliferation by inducing cell apoptosis. Our findings suggest that circulant sCD30L is functionally active and that it may favor persistence of active inflammation by inducing apoptosis of CD30(+)T cells, known to down-modulate inflammation in rheumatoid synovitis.
Department of Medicine, University of Verona, Verona, Italy.
Elisa
E
Tinazzi
Department of Medicine, University of Verona, Verona, Italy.
Alessandro
A
Barbieri
Department of Medicine, University of Verona, Verona, Italy.
Antonella
A
Rigo
Department of Medicine, University of Verona, Verona, Italy.
Giuseppe
G
Patuzzo
Department of Medicine, University of Verona, Verona, Italy.
Ruggero
R
Beri
Department of Clinical and Experimental Medicine, University of Perugia, Perugia, Italy.
Roberto
R
Gerli
Department of Medicine, University of Verona, Verona, Italy.
Giuseppe
G
Argentino
Department of Experimental Medicine, University of Genova and Institute G. Gaslini, Genova, Italy.
Antonio
A
Puccetti
Department of Medicine, University of Verona, Verona, Italy. Electronic address: claudio.lunardi@univr.it.
Claudio
C
Lunardi
D000328:Adult; D017209:Apoptosis / Q000276:immunology*; D001172:Arthritis, Rheumatoid / Q000175:diagnosis / Q000276:immunology* / Q000378:metabolism*; D053285:CD30 Ligand / Q000097:blood / Q000378:metabolism*; D005260:Female; D006801:Humans; D017730:Ki-1 Antigen / Q000097:blood / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011485:Protein Binding; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*
D053285:CD30 Ligand; D017730:Ki-1 Antigen
Apoptosis; CD30; CD30 ligand; Rheumatoid arthritis