The central event in thymic selection of T cells bearing alpha beta TCRs is their interaction with self-peptides bound to self-MHC molecules. With the use of transgenic mouse lines expressing a single peptide/MHC class II complex, we show that CD4+ T cells with the preferential usage of particular TCR V(alpha)s and V(beta)s were selected to mature on this complex in lines with the lower expression, whereas such CD4+ T cells were eliminated in the thymus in a line with the relatively high expression. When a low expressing line was crossed with a high expressing line, the frequency of CD4+ T cells selected by this complex markedly decreased. Thus, these results suggest that a single peptide/MHC class II complex, being affected by its cell surface density in the thymus, can serve as both positively and negatively selecting ligand in vivo.

The stomach region of hypocatalasemic mice of both sexes was X‐irradiated once with a dose of 20 Gy. Thirteen months after the irradiation, 3 out of 13 (20%) males and 2 out of 9 (15%) females were observed to have developed signet ring cell carcinomas in the glandular stomach. This finding was statistically significant (P < 0.01 in males and P < 0.05 in females) compared to a total absence of similar tumors in the non‐irradiated controls. Local invasion of malignant tumors into muscle and subserosal layers was observed, but no metastatic tumors were found in distant organs.

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Background Causes of extrahepatic portal vein obstruction include abdominal surgeries such as pancreaticoduodenectomy. We improved jejunal variceal bleeding due to extrahepatic portal vein occlusion after pancreaticoduodenectomy, by shunting of the testicular vein. Case presentation A 72-year-old man was diagnosed with extrahepatic bile duct cancer and underwent subtotal stomach-preserving pancreaticoduodenectomy 5 years ago. No postoperative complications occurred, adjuvant chemotherapy using gemcitabine hydrochloride was performed, and the patient remained recurrence-free. One year and 6 months post-operation, extrahepatic portal vein stenosis appeared, but no recurrence was noted. However, 4 years and 6 months later, recurrent gastrointestinal bleeding occurred, and the patient was diagnosed with an extrahepatic portal vein obstruction. Double-balloon enteroscopy showed capillary dilatation and varicose veins in the hepaticojejunostomy region, and venous bleeding from collateral blood vessels was diagnosed. A superior mesenteric vein to the right testicular vein shunt operation was performed, following which the gastrointestinal bleeding disappeared, and the anemia improved. Although transient hepatic encephalopathy occurred, conservative treatment relieved it. Double-balloon enteroscopy confirmed the disappearance of abnormal blood vessels. Conclusions A portosystemic shunt operation using the right testicular vein effectively relieved refractory variceal bleeding around the hepaticojejunostomy site in the jejunum due to an extrahepatic portal vein obstruction after pancreaticoduodenectomy.

Although T cells are educated to recognize foreign antigenic peptides in the context of self MHC molecules during their development in the thymus, peripheral T cells also recognize allo- and xeno-MHC molecules. The lower frequency of xeno-MHC-reactive T cells than that of allo-MHC-reactive T cells is often explained by the difference in the degree of homology between xeno- or allo-MHC and self MHC molecules, as well as by the species barrier of the molecules involved in immune recognition. To distinguish these two possibilities, we estimated the frequency of I-Ab-reactive CD4+ T cells selected by HLA-DQ or DR alpha E beta b molecules, using HLA-DQ6 and HLA-DRA transgenic C57BL/6 (B6) mice lacking endogenous MHC class I and/or class II molecules (DQ6A0/0 and DR alpha 30A0/0 beta 20/0). CD4+ lymph node T cells from DQ6A0/0 and DR alpha 30A0/0 beta 20/0 showed the strong proliferative response to I-Ab molecules. In addition, DQ6A0/0 and DR alpha 30A0/0 beta 20/0 rejected the skin graft from mice expressing I-Ab molecules irrespective of MHC class I expression, indicating that the CD4+ T cells recognizing I-Ab molecules are directly involved in this rejection. The estimated frequency of I-Ab-reactive CD4(+)CD8- thymocytes in DR alpha 30A0/0 beta 20/0 and DQ6A0/0 was comparable with that observed in the MHC class II-disparate strains. Our findings thus indicate that CD4+ T cells selected to mature on xeno-MHC class II molecules such as HLA-DQ6 or DR alpha E beta b, when these molecules are expressed in mice, recognize I-Ab molecules as allo-MHC class II, despite the less structural homology.