Polarity gene discs large homolog 1 regulates the generation of memory T cells

Grzegorz B. Gmyrek, Daniel B. Graham, Gabriel J. Sandoval, Gregory S. Blaufuss, Holly M. Akilesh, Keiko Fujikawa, Ramnik J. Xavier, Wojciech Swat

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

Mammalian ortholog of Drosophila cell polarity protein, Dlg1, plays a critical role in neural synapse formation, epithelial cell homeostasis, and urogenital development. More recently, it has been proposed that Dlg1 may also be involved in the regulation of T-cell proliferation, migration, and Ag-receptor signaling. However, a requirement for Dlg1 in development and function of T lineage cells remains to be established. In this study, we investigated a role for Dlg1 during T-cell development and function using a combination of conditional Dlg1 KO and two different Cre expression systems where Dlg1 deficiency is restricted to the T-cell lineage only, or all hematopoietic cells. Here, using three different TCR models, we show that Dlg1 is not required during development and selection of thymocytes bearing functionally rearranged TCR transgenes. Moreover, Dlg1 is dispensable in the activation and proliferative expansion of Ag-specific TCR-transgenic CD4+ and CD8+ T cells in vitro and in vivo. Surprisingly, however, we show that Dlg1 is required for normal generation of memory T cells during endogenous response to cognate Ag. Thus, Dlg1 is not required for the thymocyte selection or the activation of primary T cells, however it is involved in the generation of memory T cells.

Original languageEnglish
Pages (from-to)1185-1194
Number of pages10
JournalEuropean Journal of Immunology
Volume43
Issue number5
DOIs
StatePublished - Apr 2013

Keywords

  • Cell polarity
  • Discs large protein
  • Memory T cell
  • Ovalbumin
  • Transgenic T cells

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