Immunotherapeutic approaches in multiple sclerosis.

The progress in understanding the mechanisms of T cell activation, inactivation and modulation has been translated into different immunotherapeutic strategies aiming at treating multiple sclerosis (MS). Key attack points for selective immunointervention in MS include modulation of antigen recognition, costimulation blockade, induction of regulatory cells, deviation to non-pathogenic or protective responses, neutralization of proinflammatory cytokines and administration of anti-inflammatory cytokines. In addition, several attempts have been made using less specific forms of immunointervention. The two resounding successes in the immunotherapy of MS, IFN-failed and glatiramer acetate, contrast with the many attempts, equally based on sound reasoning and promising animal data. Nevertheless, antigen-based immunointervention will continue to be tested clinically, and we will certainly witness the application of more articulate strategies able to selectively target cytokine production by Th1 or Th2 cells or to modify the Th1/Th2 balance. Perhaps, an effective manipulation of pathogenic and protective cells in MS may eventually rely on a combination of antigen- and cytokine-based approaches to selectively target autoreactive T cells and divert them from autoaggression. Most importantly, new avenues are opening, such as the use of chemokine receptor antagonists, and others look very promising, as targeting dendritic cells to favour their capacity to induce regulatory T cells. Copyright 2004 Elsevier B.V.