Prevention of adjuvant arthritis by the W3/25 anti-CD4 monoclonal antibody is associated with a decrease of blood CD4(+)CD45RC(high) T cells.
Imbalance between Th1 and Th2 functions is considered to play a key role in the induction and development of several autoimmune diseases, and the correction of that imbalance has led to effective therapies of some experimental pathologies. To examine whether CD4(+)CD45RC(high) (Th1-like) and CD4(+)CD45RC(low) (Th2-like) lymphocytes play a role in the pathogenesis of adjuvant arthritis (AA) and in its prevention by anti-CD4 antibody, CD45RC expression on CD4(+) T cells was determined in arthritic rats and in animals treated with an anti-CD4 MoAb (W3/25) during the latency period of AA. The phenotype of regional lymph node lymphocytes from arthritic rats in the active phase of the disease was determined by flow cytometry. Peripheral blood lymphocytes from rats treated with W3/25 MoAb were also analysed for 2 weeks after immunotherapy finished. IgG2a and IgG1 isotypes of sera antibodies against the AA-inducing mycobacteria, considered to be associated with Th1 and Th2 responses, respectively, were also determined by ELISA techniques. Fourteen days after arthritis induction, regional lymph nodes presented an increase in CD4+CD45RC(high) T cell proportion. Preventive immunotherapy with W3/25 MoAb inhibited the external signs of arthritis and produced a specific decrease in blood CD4(+)CD45RC(high) T cells and a diminution of antibodies against mycobacteria, more marked for IgG2a than for IgG1 isotype. These results indicate a possible role of CD4(+)CD45RC(high) T lymphocytes in the pathogenesis of AA, and suggest that the success of anti-CD4 treatment is due to a specific effect on CD4(+)CD45RC(high) T subset that could be associated with a decrease in Th1 activity.
Pelegrí
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C
Department of Physiology-Division IV, Faculty of Pharmacy, University of Barcelona, Spain. cpelegri@farmacia.far.ub.es
Castell
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M
Serra
M
M
Rabanal
M
M
Rodríguez-Palmero
M
M
Castellote
C
C
Franch
A
A
D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use; D001169:Arthritis, Experimental / Q000209:etiology* / Q000276:immunology / Q000517:prevention & control; D015704:CD4 Antigens / Q000276:immunology* / Q000302:isolation & purification; D005260:Female; D017493:Leukocyte Common Antigens / Q000276:immunology* / Q000302:isolation & purification; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D009161:Mycobacterium / Q000276:immunology; D051381:Rats; D017208:Rats, Wistar; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D017493:Leukocyte Common Antigens