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  • Title: In vivo blockade of T cell development reveals alternative pathways for generation of intraepithelial lymphocytes in mice.
    Author: Mondoon S, Shibata K, Yoshikai Y.
    Journal: Immunol Lett; 2017 Nov; 191():40-46. PubMed ID: 28958836.
    Abstract:
    Intraepithelial lymphocytes (IELs) are resident cells localized within the intestinal epithelia and play an important role in regulating gut inflammations and host defense against pathogens. CD8α+ TCRαβ+ IELs are heterogeneous populations that are generated from T cell precursors including CD4- CD8α- double-negative (DN) cells and CD4+ CD8α+ double-positive (DP) cells. However, developmental pathways of TCRαβ+ IELs remained unclear. To gain insight into the mechanisms, we generated mice (Bcl11bΔDN2 mice) that lack thymic precursors (DN CD5+ TCRβ+ cells) for CD4- CD8αα+ TCRαβ+ IELs. Unexpectedly, we found that, in the absence of the precursors in thymi of Bcl11bΔDN2 mice, CD4- CD8αα+ TCRαβ+ IELs were still present in the intestine though the number was reduced. Adoptive transfer experiment showed that their precursors were highly enriched in CD8α+ TCRβ- thymocytes. The CD4- CD8αα+ TCRαβ+ IELs in Bcl11bΔDN2 mice are distinguished by Thy1.2 expression and are indeed present in WT mice. Taken together, our study reveal a novel developmental pathway for CD8αα+ TCRαβ+ IELs.
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