Egress of mature murine regulatory T cells from the thymus requires RelA.

The mechanism of egress of mature regulatory T cells (Tregs) from the thymus to the periphery remains enigmatic, as does the nature of those factors expressed in the thymic environment. In this study, we examined the fate of thymic Tregs in TNF-α/RelA double-knockout (TA-KO) mice, because TA-KO mice retain a Treg population in the thymus but have only a small Treg population at the periphery. Transplantation of whole TA-KO thymus to under the kidney capsule of Rag1-null mice failed to induce the production of donor-derived splenic Tregs expressing neuropilin-1, which is reported to be a marker of naturally occurring Tregs, indicating that TA-KO thymic Tregs either do not leave the thymus or are lost at the periphery. We next transplanted enriched TA-KO thymic Tregs to the peripheries of TA-KO mice and traced mouse survival. Transplantation of TA-KO thymic Tregs rescued the lethality in TA-KO mice, demonstrating that TA-KO thymic Tregs remained functional at the periphery. The TA-KO thymic Treg population had highly demethylated CpG motifs in the foxp3 locus, indicating that the cells were arrested at a late mature stage. Also, the population included a large subpopulation of Tregs expressing IL-7Rα, which is a possible marker of late-stage mature Tregs. Finally, TA-KO fetal liver chimeric mice developed a neuropilin-1(+) splenic Treg population from TA-KO cells, suggesting that Treg arrest was caused by a lack of RelA in the thymic environment. Taken together, these results suggest that egress of mature Tregs from the thymus depends on RelA in the thymic environment.

[A case of huge papillary adenocarcinoma of the gallbladder with marked necrosis].

A 71-year-old woman was admitted to our hospital for evaluation of a right upper abdominal tumor. A contrast-CT scan demonstrated a huge tumor extending from the hepatic hilum to the pelvic space. The rim of tumor was enhanced. The center of the tumor was not enhanced and thus considered to consist of mucus or necrotic tissues. Preoperative diagnosis as gallbladder carcinoma without infiltrating to peripheral organ was made and subsequent cholecystectomy with full-thickness dissection has been performed. The tumor itself was in a swollen gallbladder, 18 cm in diameter, consisting of necrotic tissues in the lumen. Pathologic diagnosis was papillary adenocarcinoma, classified as pHinf1a, revealing fStage II. In many cases with undifferentiated carcinoma of the gallbladder, the neoplasms grow expansively to become large tumors with marked necrosis. We report a rare case of papillary adenocarcinoma of the gallbladder presenting both a clinical course and radiologic findings indistinguishable from undifferentiated carcinoma of the gallbladder.