Decreased arthritis severity in cathepsin L-deficient mice is attributed to an impaired T helper cell compartment.
OBJECTIVE
Cathepsin L (CL) is potentially involved in joint destruction and in antigen presentation in rheumatoid arthritis. In order to define the roles of this protease in arthritis development we analysed the antigen-induced arthritis (AIA) in CL-deficient (CL(-/-)) mice.


METHODS
Antigen-induced arthritis was induced in CL(-/-) and wild-type mice. Complete CL deficiency resulted in an impaired positive selection of conventional CD4(+) T helper (Th) cells and finally in a reduced number of Th cells. Thus, we addressed the effect of this phenotype by rescuing CD4(+) Th cell numbers by transgenic expression of the human CL-like protease cathepsin V (hCV) in thymic epithelium of CL(-/-) mice [Tg(K14-hCV);CL(-/-)]. The arthritis development was monitored by measuring joint swelling. Joint inflammation and destruction were assessed histopathologically.


RESULTS
The severity of AIA was decreased in CL(-/-) mice characterized by reduced swelling, decreased inflammation and destruction, and diminished cellular and humoral immune responsiveness. AIA in Tg(K14-hCV);CL(-/-) mice was associated with a reconstitution of all parameters by normalization of the ratio of regulatory to conventional T cells.


CONCLUSIONS
Cathepsin L has a significant impact on AIA severity by influencing the selection of Th cell populations in the thymus, but seems not play any significant role in the direct joint destruction.
Institute of Pathology, University Hospital, Friedrich Schiller University, Jena, Germany. Uta.Schurigt@uni-wuerzburg.de
Uta
U
Schurigt
Rene
R
Eilenstein
Mieczyslaw
M
Gajda
Carola
C
Leipner
Lisa
L
Sevenich
Thomas
T
Reinheckel
Christoph
C
Peters
Bernd
B
Wiederanders
Rolf
R
Bräuer
D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology* / Q000473:pathology; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000473:pathology; D056668:Cathepsin L / Q000172:deficiency* / Q000235:genetics / Q000276:immunology; D002403:Cathepsins / Q000235:genetics; D003546:Cysteine Endopeptidases / Q000235:genetics; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D012710:Serum Albumin, Bovine / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D007074:Immunoglobulin G; C029180:methylated bovine serum albumin; D012710:Serum Albumin, Bovine; D002403:Cathepsins; D003546:Cysteine Endopeptidases; D056668:Cathepsin L; C117627:CTSV protein, human