title: Polarity gene discs large homolog 1 regulates the generation of memory T cells.
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.
authors: Divison of Immunobiology, Washington University School of Medicine, St Louis, MO 63110, USA.
authors: Grzegorz B
authors: GB
authors: Gmyrek
authors: Daniel B
authors: DB
authors: Graham
authors: Gabriel J
authors: GJ
authors: Sandoval
authors: Gregory S
authors: GS
authors: Blaufuss
authors: Holly M
authors: HM
authors: Akilesh
authors: Keiko
authors: K
authors: Fujikawa
authors: Ramnik J
authors: RJ
authors: Xavier
authors: Wojciech
authors: W
authors: Swat
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D019070:Cell Lineage / Q000276:immunology*; D016764:Cell Polarity; D049109:Cell Proliferation; D000074288:Discs Large Homolog 1 Protein; D015870:Gene Expression; D007156:Immunologic Memory; D019426:Integrases; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology*; D000074407:SAP90-PSD95 Associated Proteins; D060168:Thymocytes / Q000166:cytology / Q000276:immunology / Q000637:transplantation; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology
chemical_list: D000074288:Discs Large Homolog 1 Protein; C000614189:Dlg1 protein, mouse; D009419:Nerve Tissue Proteins; D011948:Receptors, Antigen, T-Cell; D000074407:SAP90-PSD95 Associated Proteins; D010047:Ovalbumin; C045073:Cre recombinase; D019426:Integrases