T-Lineage Cells Require the Thymus but Not V(D)J Recombination to Produce IL-17A and Regulate Granulopoiesis In Vivo

Abstract

IL-17A and IL-17F regulate granulopoiesis and are produced by memory T cells. Rag1−/− recombinase-activating gene-deficient mice cannot produce mature T cells but maintain normal neutrophil counts. Athymic nude mice are neutropenic or have near-normal neutrophil counts, depending on the prevailing intestinal flora, and do not produce IL-17A. By contrast, thymi from Rag1−/− mice contain as much IL-17A as those from wild-type (WT) mice. IL-17A-producing cells are found in the double negative DN1 compartment of the Rag1−/− thymus and express intracellular CD3. These cells colonize the spleen and mesenteric lymph node and secrete IL-17A in vitro following stimulation with IL-23 at a level similar to that of WT splenocytes. Adoptively transferred Rag1−/− or WT thymocytes correct neutrophil counts in neutropenic nude mice. We conclude that the development of IL-17A-producing T-lineage cells requires an intact thymic epithelium, but not V(D)J recombination.