Newly dentified members of the TNF recept or superfamily (mTNFRH1 and mTNFRH2) inhibit T-cell proliferation

By searching an EST database, we identified two TNF receptor superfamily members (named mTNFRH1 and mTNFRH2). Amino acid sequences are highly conserved between the two receptors (78% identity). The chromosomal loci of mTnfrh1 and mTnfrh2 genes are found in distal chromosome 7 in the mouse. mTNFRH1 and mTNFRH2 do not contain the cytoplasmic domain, indicating that they might function as decoy receptors. Furthermore, an alternatively spliced form of mTNFRH1 was found which contains neither the transmembrane domain nor the cytoplasmic domain, thus presumably existing as a soluble form. Northern blot analysis showed that mTnfrh1 mRNA was negligibly expressed in tissues, while mTnfrh2 mRNA was strongly expressed in spleen, lung, liver, kidney, and testis. When the extracellular domains of mTNFRH1 and mTNFRH2 were expressed in bacteria, their molecular weight of extracellular region was approximately 15 kDa. Both of the soluble forms were effective in inhibiting T-cell proliferation stimulated by anti-CD3 monoclonal antibody. Our data suggest that mTNFRH1 and mTNFRH2 may be implicated in exerting a modulatory role in the immune response.

Expression of tumor necrosis factor receptor superfamily in carotid atheroma

BACKGROUND AND OBJECTIVES: It has been reported that various inflammatory and immune reactions are involved in the development and progression of atherosclerosis. We tried to investigate whether the TNF receptor superfamilies are involved in the development and progression of atherosclerosis. MATERIALS AND METHOD: Thirteen carotid atheroma specimens(frozen sections : 10 cases, paraffin section : 5 cases) were obtained from the patients who underwent carotid endarterectomy at Samsung Medical Center and one normal aortic tissue was obtained from a transplantation donor in brain death. In the carotid endarterectomy specimens and a normal aortic tissue , the expressions of R110(TR1), 139(TR2) and DR3(TR3), members of the TNF receptor superfamilies were evaluated by immunohistochemical staining with monoclonal antibodies. Simultaneously, we evaluated the expressions of foam cells, smooth muscle cells, T-lymphocytes and B-lymphocytes. RESULTS: Immunohistochemical analysis identified a strong expressions of foam cells and smooth muscle cells in all atheroma. But, the expression of T-lymphocytes was minimal and that of B-lymphocytes was rare. The expression of DR3(TR3) was seen in all atheroma as strongly positive. The expression of 139(TR2) was observed well in frozen sections, but not in paraffin sections. Whereas, that of R110(TR1) was observed in paraffin sections as weakly positive, but not in frozen section. The areas where the TNF receptor superfamilies were expressed correlated to the area of foam cell presence. The expression of DR3 also correlated with expression of smooth muscle cells. In normal aortic tissue, the expression of inflammatory cells or TNF receptor superfamilies was not observed except smooth muscle cells which were observed in normal artery. CONCLUSION: Foam cells and smooth muscle cells were abundantly present in atheroma. The TNF receptor superfamilies are expressed in the atheroma and the region of expression was coincident with the presence of foam cells.