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t- c e l l d e v e lo p m e n t -selected CD4+ T cells DOI: 10.1038/nri2180 Two papers published in 2005 only have TEC-selected CD4+ T cells) The authors next looked at the showed that, in addition to positive and from CIITATg mice (which have role of thymocyte-selected CD4+ selection of on MHC- a mixed population of CD4+ T cells T cells in an -induced class-II-positive thymic epithelial selected on both TECs and thymo- airway model using Tg cells (TECs), human thymocytes cytes). T cells from CIITA mice a TH2‑cell-inducing . themselves express MHC class II produced both interleukin-4 (IL-4) Although thymocyte-selected + molecules and can mediate posi- andinterferon-γ (IFNγ) and at higher CD4 T cells can produce TH2-type tive selection of other thymocytes. levels compared with T cells from , CIITATg mice were less Mouse thymocytes do not express wild-type mice, showing that T cells susceptible to airway inflammation, MHC class II, so Li and colleagues from CIITATg mice have hallmarks of as shown by reduced numbers of

generated mice with MHC-class-II- both TH1 and TH2 cells. eosinophils and neutrophils in lung positive thymocytes by expressing To look at production tissue and a reduction in IgE levels the MHC class II transactivator from thymocyte-selected cells only, compared with wild-type mice. The — a transcription factor that is the authors isolated T cells from explanation for this phenomenon is required for the expression of several CIITATg mice on a CIITA-deficient not yet clear.

molecules involved in MHC class background. Even under TH1-polar- This study shows that the thymic …thymocyte- II — as a izing conditions, thymocyte-selected selection pathway influences the selected CD4+ transgene under the control of the CD4+ T cells expressed both IL-4 effector function of CD4+ T cells and Tg T cells retain Cd4 promoter (termed CIITA and IFNγ. Bone-marrow chimaera suggests that further studies might mice). The current study shows that experiments further substantiated be warranted to address the role of characteristics by comparison to TEC-selected these results. Strikingly, even though thymocyte-selected CD4+ T cells in of both CD4+ T cells, thymocyte-selected the signal transducer and activator immune responses in humans. T helper 1 CD4+ T cells retain characteristics of of transcription 6 (STAT6) signalling Elaine Bell both T helper 1 (T 1) and T 2 cells. pathway is crucial in T 2-cell differ- (T 1) and T 2 H H H ORIGINAL RESEARCH PAPER Li, W. et al. H H The authors first compared entiation, thymocyte-selected CD4+ Thymic selection pathway regulates the cells. effector function of CD4 T cells. J. Exp. Med. cytokine production from T cells T cells from Stat6-knockout mice 204, 2145–2157 (2007) isolated from wild-type mice (which were able to produce IL-4.

nature reviews | volume 7 | october 2007 © 2007 Nature Publishing Group