Deficient antigen presentation by thymic epithelial cells reveals differential induction of T cell clone effector functions by CD28-mediated costimulation.
Thymic epithelial cells participate in tolerance induction by deleting or inducing anergy of autoreactive lymphocytes. To explore this process in vitro, the antigen-presenting function of thymic epithelial cell lines was evaluated using a panel of T hybridoma and cloned cells displaying the same antigenic specificity. These mouse thymic epithelial cell lines could process different exogenous antigens and stimulate T hybridoma cells but only induced a partial activation of helper cloned T cells. This state of incomplete activation was characterized by the inability to produce IL-2 and IFN-gamma upon antigenic stimulation, whereas T cell IL-2R alpha expression and cytolytic potential were optimally induced. Thymic epithelial cells failed to express CD28 ligands detected by a CTLA-4/Ig probe even after induction by IFN-gamma. Optimal cloned T cell activation was only observed in the presence of LPS blasts or exogenous IL-2. Costimulation with anti-CD28 mAb was found to restore IFN-gamma but not IL-2 production. Thus, T cell activation by thymic epithelial cell lines provides a useful model to further dissect the requirements for costimulatory molecules, which, in addition to CD28, are required for optimal T cell activation.
Lepesant
H
H
Centre d'Immunologie INSERM-CNRS de Marseille-Luminy, France.
Pierres
M
M
Naquet
P
P
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000938:Antigen-Presenting Cells / Q000276:immunology*; D018106:CD28 Antigens / Q000276:immunology* / Q000494:pharmacology; D002460:Cell Line; D002999:Clone Cells; D004848:Epithelium / Q000276:immunology; D006825:Hybridomas; D007371:Interferon-gamma / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology*
D000911:Antibodies, Monoclonal; D018106:CD28 Antigens; D007371:Interferon-gamma