The role of CD40 in peripheral T cell tolerance and immunity

CD40 and CD40 ligand (CD40L) have been implicated as important molecules fo r the transformation of nonactivated antigen-presenting cells (APC) into ce lls that are potent inducers of cytotoxic T lymphocyte (CTL) immunity. The onset of a successful immune re -sponse lies within the control of the CD4( +) T helper cells which, after specific antigen recognition, can up-regulat e CD40L and subsequently activate APC through CD40 signaling. Triggering of CD40 with antibodies in vivo can replace the need for CD40L-expressing CD4 (+) T helper cells for cross-priming of CTL. Blocking of CD40-CD40L interac tions can also have profound effects on the generation of T cell immunity. Interesting ly, differential involvement of CD40/CD40L in immune responses can be observed between various immunological sites in the body. In most si tes of the periphery interruption of CD40-CD40L interactions can lead to th e induction of T cell tolerance whereas in mucosal tissues this interruptio n can lead to abrogation of T cell tolerance. Furthermore, in vivo CD40 act ivation can convert specific T cell tolerance following peptide vaccination into efficient T cell priming. Thus intervention of CD40-CD40L interaction s can result in enhancement or down-modulation of T cell reactivity and the refore modulation of these interactions may form the foundation of new trea tment modalities directed against malignancies, allergies, organ rejections and autoimmunity.