Subject(s)
Gingivitis, Necrotizing Ulcerative/etiology , Palate, Hard , Sialometaplasia, Necrotizing/diagnosis , Biopsy , Diagnosis, Differential , Gingivitis, Necrotizing Ulcerative/diagnosis , Gingivitis, Necrotizing Ulcerative/pathology , Humans , Male , Middle Aged , Mouth Mucosa/pathology , Palate, Hard/pathology , Sialometaplasia, Necrotizing/pathologySubject(s)
Antibodies, Monoclonal , Antibodies, Monoclonal/therapeutic use , Dermatologic Agents/therapeutic use , Skin Diseases, Vesiculobullous/drug therapy , Tumor Necrosis Factor-alpha , Aged , Antibodies, Monoclonal/administration & dosage , Arm , Breast Neoplasms/surgery , C-Reactive Protein , Dermatologic Agents/administration & dosage , Female , Humans , Infliximab , Infusions, Intravenous , Leukocyte Count , ThoraxABSTRACT
The individual roles of the two TNFRs on dendritic cells (DC) are poorly understood. Investigating bone marrow-derived DC from TNFR-deficient mice, we found that cultures from TNFR1(-/-) mice continue to form proliferating clusters for 6-9 mo. In contrast, DC derived from wild-type, TNFR2(-/-), or TNFR1/2(-/-) mice survived for only 3-4 wk. DC obtained from these TNFR1(-/-) long term cultures (LTC) mice show an unusual mixed immature/mature phenotype. The continuous proliferation of the LTC is GM-CSF dependent and correlates with decreased protein levels of the cyclin-dependent kinase inhibitors p27(KIP1) and p21(CIP1). Prolonged survival of TNFR1(-/-) DC appears to be independent from NF-kappaB and Bcl-2 pathways and is rather enabled by the down-regulation of CD95, resulting in the resistance to CD95 ligand-induced apoptosis. These data point to proapoptotic signals mediated via TNFR1 and antiapoptotic signals mediated via TNFR2 in DC.