Immunomodulation

Abstract

La connaissance des mécanismes d'activation et d'amplification de la réponse immunitaire ouvre un champ de la médecine dont l'immunomodulation est une application potentielle. En inhibant la prolifération des lymphocytes, nombre d'immunosuppresseurs bloquent l'induction d'une tolérance immunitaire. Celle-ci est précisément l'objectif d'approches ciblant les structures de reconnaissance de l'antigène, de co-stimulation ou les cytokines. Une caractérisation moléculaire des états fonctionnels auxquels conduit l'activation lymphocytaire est aujourd'hui accessible, et susceptible d'ouvrir la voie à la définition de nouvelles cibles thérapeutiques de l'immunomodulation.

The study of activation and amplification mechanisms that characterize immune responses is a key contribution to immunomodulation. Many immunosuppressive drugs which target calcineurin inhibit lymphocyte proliferation. This precludes inducing immune tolerance which, however, is an unquestionned goal of clinical immunology. New strategies focus on inducing immune tolerance by interfering with structures involved in antigen recognition either on antigen presenting cells or on lymphocytes. Targetting the T cell receptor and associated structures (CD3, CD4, CD8) or antigen presenting structures (major histocompatibility complex class II molecules) has proved efficient in inducing tolerance. Altered peptides ligands has seemingly been developed in order to interfere with T cell activation through the T cell receptor. Other approaches include targetting costimulatory structures (CD28/B7, CD40/CD40 ligand) or regulatory circuits involving cytokines, chemokines and their receptors. The molecular characterization of activated and tolerant lymphocytes is an achievable goal that will help defining new targets of immunomodulation in the coming years.