Intrathymic presentation by dendritic cells and macrophages: their role in selecting T cells with specificity for internal and external nominal antigen

Abstract

The present study focused on the question of whether intrathymic dendritic cells and macrophages (DC/M phi) are involved in the processes of T-cell repertoire selection and establishment of tolerance towards nominal antigen. Proliferation of thymocytes (TC) was determined under limiting dilution (LD) conditions after depletion of DC/M phi and after reconstitution of TC, which were depleted of cells expressing major histocompatibility complex (MHC) class II antigens, with thymic DC/M phi. Trinitrophenyl (TNP) [coupled to ovalbumin (OVA)] was used as an internal antigen in prenatally trinitrobenzenesulphonic acid (TNBS)-treated mice and as an external antigen in prenatally untreated mice. Intrathymic DC/M phi were clearly involved in selecting the repertoire of T cells specific for external antigen: they presented the antigen and initiated proliferation of thymic T cells, which were depleted of MHC class II antigen-expressing cells. But they were not the only cells to present nominal antigen in the thymic environment. Intrathymic DC/M phi could also deliver negative signals. This became apparent when evaluating presentation of TNP in prenatally TNBS-treated mice. Thymus-derived DC/M phi from prenatally TNBS-treated mice could not initiate proliferation of TC in response to TNP-OVA. Instead, when prenatally TNBS-treated mice received an antigenic challenge [TNP-sheep red blood cells (SRBC)], thymic DC/M phi inhibited proliferation of cortisone-resistant TC from untreated and prenatally TNBS-treated mice. This can be explained by assuming that in the process of establishing tolerance, intrathymic DC/M phi may exert cytotoxic/cytostatic activity.