ABSTRACT
The terminal fate of dendritic cells (DC) remains relatively uncertain. In this study, we tested the hypothesis that DC undergo apoptosis after Ag-specific interaction with T cells. When splenic DC isolated from BALB/c mice were cocultured with HDK-1 T cells (a keyhole limpet hemocyanin (KLH)-specific CD4+ Th1 clone) in the presence of KLH, they showed conspicuous cell death as measured by propidium iodide (PI) uptake and chromatin condensation, whereas they remained relatively intact when incubated with either T cells or KLH alone. Likewise, the long term DC line XS52, which was established from BALB/c mouse epidermis, also died rapidly (within 2 h), and they exhibited characteristic DNA laddering when cocultured with HDK-1 T cells in the presence of KLH. RT-PCR and FACS analyses revealed the expression of CD95 (Fas) by XS52 DC and of CD95 ligand (CD95L) (Fas ligand) by activated HDK-1 T cells, suggesting a functional role for these molecules. In fact, anti-CD95L mAb inhibited partially (50%) T cell-mediated XS52 cell death, and coupling of surface CD95 with anti-CD95 mAb triggered significant XS52 cell death, but only in the presence of cycloheximide. Thus, ligation of CD95 (on DC) with CD95L (on T cells) is one, but not the only, mechanism by which T cells induce DC death. Finally, DC isolated from the CD95-deficient mice were found to be significantly more efficient than DC from control mice in their capacity to induce delayed type hypersensitivity responses in vivo. We propose that T cell-induced DC apoptosis serves as a unique down-regulatory mechanism that prevents the interminable activation of T cells by Ag-bearing DC.
Subject(s)
Apoptosis/immunology , CD4-Positive T-Lymphocytes/immunology , Dendritic Cells/immunology , Epitopes, T-Lymphocyte/immunology , Animals , CD4-Positive T-Lymphocytes/metabolism , Cell Death/immunology , Cell Line , Dendritic Cells/cytology , Epitopes, T-Lymphocyte/metabolism , Fas Ligand Protein , Female , Hypersensitivity, Delayed/immunology , Ligands , Membrane Glycoproteins/physiology , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Mice, Inbred MRL lpr , Spleen/cytology , fas Receptor/genetics , fas Receptor/metabolism , fas Receptor/physiologyABSTRACT
OBJECTIVES: To develop interactive teaching mechanisms for an "Introduction to Dermatology" course for medical students and to compare the effectiveness and impact of these mechanisms on learning. DESIGN: Survey and before-after trial. SETTING: Medical school. PARTICIPANTS: Second-year medical students (approximately 200 per year). MAIN OUTCOME MEASURES: The teaching mechanisms were evaluated through responses to questionnaire-based course evaluations (survey). The impact of the CD-ROM program was assessed by performance in Kodachrome slide-based multiple choice examinations (before-after trial). RESULTS: Overall the course was highly rated and among its components, the live-patient sessions, the CD-ROM program, and the poster exhibit were rated most effective. There was no difference in the examination performance of students who took the course before and after inclusion of the CD-ROM program. High-scoring students attended a significantly greater number of lectures in comparison with low-scoring students. CONCLUSIONS: The 3 teaching mechanisms judged by students to be most effective were also the most visual and interactive, suggesting that these attributes are critical to learning dermatology. On the other hand, addition of the CD-ROM program failed to produce differential improvement in short-term cognitive skills.
