TY - JOUR
T1 - T-lineage cells require the thymus but not V(D)J recombination to produce IL-17A and regulate granulopoiesis in vivo
AU - Smith, Emily
AU - Von Vietinghoff, Sibylle
AU - Stark, Matthew A.
AU - Zarbock, Alexander
AU - Sanders, John M.
AU - Duley, Amanda
AU - Rivera-Nieves, Jesus
AU - Bender, Timothy P.
AU - Ley, Klaus
PY - 2009/11/1
Y1 - 2009/11/1
N2 - 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 nearnormal 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.
AB - 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 nearnormal 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.
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U2 - 10.4049/jimmunol.0900887
DO - 10.4049/jimmunol.0900887
M3 - Article
C2 - 19843951
AN - SCOPUS:77954147117
SN - 0022-1767
VL - 183
SP - 5685
EP - 5693
JO - Journal of Immunology
JF - Journal of Immunology
IS - 9
ER -