IL-15 supports the generation of protective lung-resident memory CD4 T cells.

Tissue-resident memory T cells (TRM) provide optimal defense at the sites of infection, but signals regulating their development are unclear, especially for CD4 T cells. Here we identify two distinct pathways that lead to the generation of CD4 TRM in the lungs following influenza infection. The TRM are transcriptionally distinct from conventional memory CD4 T cells and share a gene signature with CD8 TRM. The CD4 TRM are superior cytokine producers compared with conventional memory cells, can protect otherwise naive mice against a lethal influenza challenge, and display functional specialization by inducing enhanced inflammatory responses from dendritic cells compared with conventional memory cells. Finally, we demonstrate than an interleukin (IL)-2-dependent and a novel IL-2-independent but IL-15-dependent pathway support the generation of cohorts of lung TRM.

The metabolism of salicylidene benzylamine, a pro-drug for salicylate, in rats and dogs.

1. Oral doses of [14C]salicylidene benzylamine were well absorbed by rats and dogs and excreted mainly in the urine (92% dose by rat in 24 h and 84% by dog in 48 h). 2. After 50, 100 and 300 mg/kg oral doses to rats, peak mean plasma 14C concn. (mainly salicylic acid) of 77, 243 and 396 micrograms equiv./ml respectively were reached between 2 and 4 h and maintained at this level until about 7.5 h. 14C was cleared more rapidly from the plasma of male rats than from that of female rats. After 44, 85 and 300 mg/kg oral doses to dogs, peak mean plasma 14C concn. (mainly salicylic acid) of 114, 194 and 320 micrograms equiv./ml respectively were reached at 4 h and then declined with a half-life of 6-7 h. 3. Tissue 14C concn. in both species were greatest at the times of peak plasma 14C concn., but in general were lower than those in the corresponding plasma. 4. The major components in rat and dog urine were salicyl alcohol, salicylic acid and salicyluric acid, the first two being excreted partly as glucuronic acid/sulphate conjugates. After initial hydrolysis of salicylidene benzylamine to salicylaldehyde, approximately equal amounts were reduced and oxidized to the corresponding alcohol and acid respectively.