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Type 2 T helper (T(H)2) cells are protective against parasitic worm infections but also aggravate allergic inflammation. Although the role of dendritic cells (DCs) in T(H)2 cell differentiation is well established, the underlying mechanisms are largely unknown. Here, we show that DC induction of T(H)2 cells depends on membrane-associated RING-CH-1 (MARCH1) ubiquitin ligase. The pro-T(H)2 effect of MARCH1 relied on lymph node (LN)–resident DCs, which triggered T cell receptor (TCR) signaling and induced GATA-3 expression from naïve CD4(+) T cells independent of tissue-driven migratory DCs. Mice with mutations in the ubiquitin acceptor sites of MHCII and CD86, the two substrates of MARCH1, failed to develop T(H)2 cells. These findings suggest that T(H)2 cell development depends on ubiquitin-mediated clearance of antigen-presenting and costimulatory molecules by LN-resident DCs and consequent control of TCR signaling.

• Sixty-three children from 2 to 12 years of age were studied by means of brain stem evoked potentials (BEP) and otoscopic evaluation in a preliminary assessment of the sensitivity of BEP latency measures to middle ear abnormality. Wave I proved to be the most sensitive component; 81.25% of subjects with acute suppurative otitis media and 62.50% of subjects with secretory otitis media demonstrated latencies prolonged by more than 1 SD beyond the values observed in normal control subjects. Of the same subject groups, 86.21% and 93.31% demonstrated wave I latencies within normal limits upon retesting after the otitis had resolved. The BEP technique permitted identification of several subjects with abnormal audiometric findings despite normal otoscopy. There are implications for use of the BEP as a clinical adjunct to traditional methods of auditory assessment. (Arch Otolaryngol105:17-20, 1979)