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Two distinct Th9 subpopulations are generated by activating naïve CD4 cells either by antigen/APC or anti-CD3/CD28 antibodies

Wednesday, October 26, 2011 — Poster Session IV

2:00 p.m. – 4:00 p.m.

Natcher Conference Center

NEI

IMMUNO/INFLAM-27

Authors

  • C Tan
  • B Vistica
  • L Nugent
  • G Shi
  • I Gery

Abstract

Recent studies identified and partially characterized the lymphocyte Th9 lineage, using anti- CD3/CD28 antibodies for activation during polarization. Using TCR transgenic mice we showed, however, that Th9 are also generated by activation with the specific antigen, hen egg lysozyme (HEL) (J. Imm., 2010). Here, we compared Th9 lines generated by either HEL and APC, or anti-CD3/CD28 antibodies, but similarly polarized by IL-4/TGF-β. Main observations: (i) IL-9 and IL-10 are similarly secreted in the supernatant by HEL or antibody-activated cultures. Intracellular IL-9 is expressed earlier in the antibody-activated cells, but IL-10 is similarly produced by the two subsets. (ii) Both subsets induced ocular inflammation when adoptively transferred into mice expressing HEL in their eyes, but pathogenicity of antigen-stimulated Th9 was restricted to day three in culture, whereas antibody-stimulated Th9 induced disease when collected after three-five days in culture. (iii) The two Th9 subsets expressed similarly the majority of tested major surface antigens, but differed in expression of CD45RB, CD69, α4β7 and αEβ7. (iv) The two Th9 subsets differed remarkably in their expression of several chemokine and chemokine receptor transcripts. Thus, different modes of activation of naïve CD4 cells during polarization yield two distinct subpopulations of Th9.

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