Oral immunomodulation therapy in rheumatoid arthritis

Because the gastrointestinal mucosa is a vast interface between the body an d the environment, it is the main entry site for many environmental antigen s. Enterocytes can cleave environmental antigens into peptides, bind these peptides to their CD1 receptor, and present them to T cells. intact antigen s can penetrate through specialized Peyer's patch enterocytes called 'M cel ls'; they are then degraded and presented by dendritic cells to Peyer's pat ch T cells. The influx of multiple antigens through the gastrointestinal mu cosa usually results in tolerance. High-dose tolerance is due to T cell: de letion or anergy, whereas low-dose tolerance involves activation of TGF bet a -producing Th2 or Th3 cells. TGF beta inhibits lymphocyte proliferation a nd the production of antibodies to ingested antigens; in addition, it block s the proliferation of lymphocytes in organs to which gastrointestinal Th3 lymphocytes migrate. This 'innocent bystander' effect has been used to try to induce oral tolerance. For instance, pretreatment with oral bovine type II collagen has proved capable of modulating several models of experimental polyarthritis. Arthritis severity was considerably reduced. Preliminary at tempts in humans with rheumatoid arthritis have yielded promising results. (C) 2000 Editions scientifiques et medicales Elsevier SAS.