CD8 T-lymphocyte-mediated regulation of ovalbumin-specific murine IgE responses.
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Biomedical subjects
Publications and source records attributed to M J Thomas.
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BACKGROUND: It is well recognized that CD8 T cells inhibit IgE responses. In this study, we investigated the mechanism of CD8 T cell-mediated IgE suppression by comparing the capacity of T cytotoxic 1 (Tc1) and T cytotoxic 2 (Tc2) CD8 T cells to inhibit IgE responses to ovalbumin (OVA). METHODS: Tc1 and Tc2 CD8 T cells were generated from OVA(257-264)-specific Vbeta5.2 T cell receptor (TcR) transgenic mice by stimulation with anti-CD3 and anti-CD28 under Tc1 and Tc2 polarizing conditions. Tc1 and Tc2 Vbeta5.2 TcR CD8 T cells (10(6)) were adoptively transferred to syngeneic mice, and following immunization with 100 micro of OVA/alum, serum IgE antibodies were measured by passive cutaneous anaphylaxis and expressed as the highest dilution that gave a detectable skin response. RESULTS: Both Tc1 and Tc2 CD8 T cells from OT-I mice inhibited IgE. CONCLUSION: Both Tc1 and Tc2 CD8 T cells promote Th1 immunity and inhibit IgE responses. This process appears to be independent of CD8 T cell-derived IFN-gamma, as both Tc2 (IFN-gamma-) and Tc1 (IFN-gamma+) CD8 T cells inhibited IgE.
Based on histological, immunohistochemical, and ultrastructural studies, it is now apparent that the modified myoepithelial cell component of pleomorphic adenomas has a considerable range of cytological features. We reasoned that myoepitheliomas could be tumors with a similar spectrum of neoplastic myoepithelium but lacking the ductal element displayed in pleomorphic adenomas. A review of available salivary gland tumors identified 40 examples based on this definition. Architecturally, these myoepitheliomas displayed either nonmyxoid (solid), myxoid (pleomorphic adenoma-like), reticular (canalicularlike), or mixed growth patterns, while cytologically the lesions were composed of spindle-type (32.5%), hyaline-type (7.5%), epithelial-type (45.0%), clear-type (2.5%), or mixed-type (12.5%) tumor cells. Electron microscopy was carried out on eight examples and detailed immunohistochemistry on two methanol-fixed cases. As a result of the current review of myoepitheliomas and the description of similar lesions in the literature, it is our contention that salivary gland myoepitheliomas are not as rare as has been purported.
During ultrastructural examination of a difficult to diagnose tumor, short spacing collagen fibrils (periodicity of banding, approximately 43.2 nm) and native collagen fibrils (periodicity of banding, approximately 53 nm) were found in dilated and vacuolated cisternae of rough endoplasmic reticulum and the perinuclear cistern. Original diagnoses from several histopathologists included alveolar soft part sarcoma, malignant fibrous histiocytoma, atypical fibroxanthoma, and myogenic tumor. The finding of intracisternal collagen (which is but a variety of intracellular collagen) led to the conclusion that this was a fibroblastic neoplasm. This, plus a review of the histologic findings, led to the diagnosis of proliferative fasciitis and myositis of childhood.
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Accurate measurement of sex hormone binding globulin (SHBG) by 5 alpha-dihydrotestosterone (DHT) binding assays requires the establishment of acceptable upper and lower limits of labelled DHT binding and the use of optimal quantities of radioinert DHT to displace labelled DHT. A computer assisted binding assay for SHBG is described in which upper and lower binding limits are derived mathematically from analysis of labelled DHT binding to eight concentrations of SHBG in the range 25 to 400 nM. The optimal quantity of radioinert DHT for a given SHBG concentration is also derived from these binding curves. A computer program determines whether or not, in a given sample, the binding of labelled DHT falls within these established binding limits and also calculates the concentration of SHBG. This technique reduces the number of tubes required in an assay and provides rapid validation and calculation of results.
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The role of gastrointestinal digestive processes in the systemic availability of ingested protein antigens was examined by feeding the trypsin inhibitor aprotinin intragastrically to mice and measuring uptake of ovalbumin and 14C-polyethylene glycol (MW 4000) from the gastrointestinal tract. Trypsin and chymotrypsin activities in the intestinal lumen were significantly reduced by aprotinin feeding. Aprotinin slowed stomach emptying, but radioimmunoassays for immunoreactive ovalbumin in the serum of mice prefed aprotinin showed 12-fold elevations within 1 hr after ovalbumin feeding. Uptake of a nonmetabolized macromolecular probe, 14C-polyethylene glycol-4000, increased less than two-fold when fed with aprotinin under the same conditions, indicating that the increased uptake of immunoreactive ovalbumin was not due to changes in intestinal permeability. The results show that inhibition of luminal proteolysis caused significant increases in the serum concentration of immunoreactive ovalbumin, indicating that acute inhibition of luminal proteases permits larger quantities of relatively intact protein to interact with mucosal absorptive surfaces. These results support the hypothesis that pancreatic proteases modulate antigen absorption from the lumen in adult animals.