both maturation and survival of human dendritic cells are impaired in the presence of anergicsuppressor t cells成熟和树突细胞生存的人类都在anergicsuppressor t细胞受损.pdfVIP

Clinical Developmental Immunology, March 2003, Vol. 10 (1), pp. 61–65 Both Maturation and Survival of Human Dendritic Cells are Impaired in the Presence of Anergic/Suppressor T Cells a, ` a b a L. FRASCA *, C. SCOTTA , G. LOMBARDI and E. PICCOLELLA aDepartment of Cell Development and Biology, “La Sapienza” University, Via dei Sardi, 70 - 00185, Rome, Italy; bDepartment of Immunology, Imperial College of Medicine, Hammersmith Hospital, W12 0NN, London, UK T cell suppression is a well established phenomenon, but the mechanisms involved are still a matter of debate. Mouse anergic T cells were shown to suppress responder T cell activation by inhibiting the antigen presenting function of DC. In the present work we studied the effects of co-culturing human anergic CD4þ T cells with autologous dendritic cells (DC) at different stages of maturation. Either DC maturation or survival, depending on whether immature or mature DC where used as APC, was impaired in the presence of anergic cells. Indeed, MHC and costimulatory molecule up-regulation was inhibited in immature DC, whereas apoptotic phenomena were favored in mature DC and consequently in responder T cells. Defective ligation of CD40 by CD40L (CD154) was responsible for CD95- mediated and spontaneous apoptosis of DC as well as for a failure of their maturation process. These findings indicate that lack of activation of CD40 on DC by CD40L-defective anergic cells might be the primary event involved in T cell suppression and support the role of CD40 signaling in regulating both