Prevention of adjuvant arthritis by the W3/25 anti-CD4 monoclonal antibodyis 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 corr ection of that imbalance has led to effective therapies of some experimenta l pathologies. To examine whether CD4(+)CD45RC(high) (Th1-like) and CD4(+)C D45RC(low) (Th2-like) lymphocytes play a role in the pathogenesis of adjuva nt arthritis (AA) and in its prevention by anti-CD4 antibody, CD45RC expres sion on CD4(+) T cells was determined in arthritic rats and in animals trea ted with an anti-CD4 MoAb (W3/25) during the latency period of AA. The phen otype of regional lymph node lymphocytes from arthritic rats in the active phase of the disease was determined by flow cytometry. Peripheral blood lym phocytes from rats treated with W3/25 MoAb were also analysed for 2 weeks a fter immunotherapy finished. IgG2a and IgG1 isotypes of sera antibodies aga inst the AA-inducing mycobacteria, considered to be associated with Th1 and Th2 responses, respectively, were also determined by ELISA techniques. Fou rteen days after arthritis induction, regional lymph nodes presented an inc rease in CD4(+)CD45RC(high) T cell proportion. Preventive immunotherapy wit h W3/25 MoAb inhibited the external signs of arthritis and produced a speci fic decrease in blood CD4(+)CD45RC(high) T cells and a diminution of antibo dies against mycobacteria, more marked for IgG2a than for IgG1 isotype. The se 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 as sociated with a decrease in Th1 activity.