Effective treatment of adjuvant arthritis with a stimulatory CD28-specific monoclonal antibody.
OBJECTIVE
To determine the immunomodulatory effects of the anti-rat CD28 monoclonal antibody (Mab) JJ316 on the onset of rat adjuvant arthritis (AA). JJ316 is a superagonistic Mab that induces polyclonal T cell proliferation in the absence of T cell receptor (TCR) ligation and promotes the expansion of regulatory T cells.


METHODS
Female Wistar rats in which AA was induced were treated with JJ316 on Day 0 and Day 9 postinduction. A parallel treatment with JJ319, a "conventional" CD28-specific Mab that costimulates anti-TCR triggered proliferation, was performed. Severity of arthritis was monitored by means of an arthritic score, and by recording hindpaw volume and body weight increases. Serum antibodies against the AA-inducing mycobacteria were also determined by ELISA. To ascertain the effect of JJ316 on T lymphocytes in vivo, blood CD4+CD45RChigh (Th1-like) and CD4+CD45RClow (Th2-like) cells were analyzed by flow cytometry, and the relative levels of interleukin 2 (IL-2), IL-10, and interferon-g (IFN-g) mRNA in synovial tissue were measured by real-time reverse transcription-polymerase chain reaction.


RESULTS
JJ316 efficiently prevented the inflammatory process of AA. This effect was associated with a specific decrease in the blood CD4+CD45RChigh/CD4+CD45RClow T cell ratio and high IL-10 mRNA expression in the synovia. In addition, anti-mycobacteria antibody levels decreased in JJ316 treated animals. In contrast, administration of the conventional anti-CD28 Mab JJ319 did not improve inflammation.


CONCLUSIONS
JJ316, a stimulatory CD28-specific Mab known to promote Th2 function and the expansion of regulatory T cells, provides effective protection from AA.
Rodríguez-Palmero
Marta
M
Department of Physiology, Faculty of Pharmacy, University of Barcelona, Barcelona, Spain.
Franch
Angels
A
Castell
Margarida
M
Pelegrí
Carme
C
Pérez-Cano
Francisco J
FJ
Kleinschnitz
Christoph
C
Stoll
Guido
G
Hünig
Thomas
T
Castellote
Cristina
C
D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000942:Antigens, Bacterial / Q000276:immunology; D001169:Arthritis, Experimental / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D018106:CD28 Antigens / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D002452:Cell Count; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005260:Female; D006614:Hindlimb / Q000187:drug effects / Q000473:pathology; D007155:Immunologic Factors / Q000627:therapeutic use*; D009161:Mycobacterium / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D013583:Synovial Membrane / Q000187:drug effects / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000473:pathology
D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; D000942:Antigens, Bacterial; D018106:CD28 Antigens; D016207:Cytokines; D007155:Immunologic Factors; D012333:RNA, Messenger