Costimulatory molecules CD80 and CD86 in the rat; tissue distribution and expression by antigen-presenting cells

The CD28-CD80/CD86 costimulatory pathway provides a critical signal for T c ell activation. Only recently rat CD80 and CD86 have been cloned and monocl onal antibodies have been generated. In this study we examined the expressi on of these molecules in lymphoid tissue and on purified subsets of antigen -presenting cells (APC), The target tissue of cyclosporin A-induced autoimm unity, i.e. the skin and tongue, were also examined for expression of CD80 and CD86, Whereas CD80 was hardly detected in the lymphoid tissues, CD86 wa s clearly expressed by non-lymphoid cells in the thymus, as well as in the secondary lymphoid organs. With respect to lymphoid cells, only germinal ce nter B cells exhibited clear CD86 expression. Phenotypic analysis by flow c ytometry revealed that only dendritic cells, both of thymic and splenic ori gin, expressed the full array of stimulatory molecules required for the pro per activation of naive T cells. On development of cyclosporin A-induced au toimmunity, non-professional APC, i.e. epithelial cells, started to express MHC class II, but not the costimulatory ligands CD80 and CD86, However, CD 86 staining was observed in the target tissue and was associated with Lange rhans cells as well as infiltrating leukocytes, Altogether, our results sho w that also in the rat strong stimulatory capacity for primary immune respo nses is associated with the expression of the costimulatory ligands CD80 an d CD86, As concluded from the in situ expression CD86 may be the predominan t costimulatory ligand early in immune responses.