Immunological tolerance in the therapy of rheumatoid arthritis.

Dramatic progress in the treatment of Rheumatoid Arthritis (RA) has led to an early and aggressive treatment strategy, combining DMARDS with biological agents. Since these therapies are able to induce initial clinical control, attention has shifted toward the maintenance of this state. Tools to maintain long-term remission are still lacking but may be found in the ability to establish immunological tolerance. Tolerance can be induced in several specific and nonspecific ways, including manipulation of costimulatory signals, induction of regulatory T cells, and tolerization to heat shock proteins. Induction of disease control with the current combination therapies, followed by progressive withdrawal in parallel with re-establishing immunological tolerance, may be an attractive approach in the near future.