Although the fetal immune system is considered tolerogenic, preterm infants can suffer from severe intestinal inflammation, including necrotizing enterocolitis (NEC). Here, we demonstrate that human fetal intestines predominantly contain tumor necrosis factor-a (TNF-a) + CD4 + CD69 + T effector memory (Tem) cells. Single-cell RNA sequencing of fetal intestinal CD4 + T cells showed a T helper 1 phenotype and expression of genes mediating epithelial growth and cell cycling. Organoid co-cultures revealed a dosedependent, TNF-a-mediated effect of fetal intestinal CD4 + T cells on intestinal stem cell (ISC) development, in which low T cell numbers supported epithelial development, whereas high numbers abrogated ISC proliferation. CD4 + Tem cell frequencies were higher in inflamed intestines from preterm infants with NEC than in healthy infant intestines and showed enhanced TNF signaling. These findings reveal a distinct population of TNF-a-producing CD4 + T cells that promote mucosal development in fetal intestines but can also mediate inflammation upon preterm birth.

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Objective• To test the clinical and sonographic predictors of testicular torsion (TT) with the aim of reducing negative exploration rates. Patients and Methods• We performed a prospective study of all boys treated for 'acute scrotum' at our institute between January 2001 and April 2012 and clinical findings were documented.• If available, ultrasonography (US) was added to the diagnostic evaluation.• A prediction of the diagnosis was based on clinical and sonographic features, and was followed by surgical exploration in all patients. Results• A total of 104 patients were included in the 16-month period of the study.• No single finding excluded TT. The clinical features (pain <24 h, nausea/vomiting, abnormal cremasteric reflex, high position of the testis) appeared predictive (100% sensitivity) and the clinical scoring system was proven to be reliable, reducing the negative exploration rate by >55%.• Ultrasound predictors alone were not able to identify all boys with TT. Conclusions• It is safe to refrain from routine surgical exploration in every child with acute scrotum if the clinical score is applied, which results in a marked reduction of negative explorations.• A reliable diagnosis could not be obtained based on US alone. As scrotal US is unpleasant for the child, we propose to refrain from this if the clinical score is positive. Patients with a negative clinical score are suitable candidates for US to establish and secure diagnosis.