CTLA4Ig and the therapeutic potential of T cell co-stimulation blockade.
It is now generally accepted that CD4 T cells are critical players in the initiation of adaptive immune responses by contributing to the terminal differentiation of effector B cells or CD8+ T cells. It is therefore not surprising that CD4+ T cell activation is tightly controlled through the concerted action of a large number of molecular interactions. Activation requires not only the recognition of the appropriate antigen within a MHC molecule by the T cell receptor TCR but also the delivery of co-stimulatory signals by the antigen presenting cell APC . As a consequence therapeutic modulation of co-stimulatory molecules for instance with CTLA4Ig can lead to interference with T cell activation and consequently abrogation of pro-inflammatory manifestations mediated by cell types influenced by CD4+ T cells such as B cells CD8+ T cells or macrophages. This type of observations provided the rationale for the use of co-stimulatory blockade in autoimmunity and other immunopathology characterized by inappropriate immune activation such as rheumatoid arthritis RA . Several studies have also suggested that besides the non-specific anti-inflammatory effects co-stimulation blockade may in certain conditions promote the induction of long term immune tolerance.
Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal. lgraca@fm.ul.pt
Luis
L
Graca
D000069594:Abatacept; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology*; D016207:Cytokines / Q000502:physiology; D006801:Humans; D018796:Immunoconjugates / Q000627:therapeutic use*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology*
D018501:Antirheumatic Agents; D016207:Cytokines; D018796:Immunoconjugates; D000069594:Abatacept