title: The Microtubule-Associated Protein Lis1 Regulates T Lymphocyte Homeostasis and Differentiation.
abstract: The microtubule-associated protein lissencephaly 1 (Lis1) is a key regulator of cell division during stem cell renewal and differentiation. In this study, we examined the role of Lis1 in T lymphocyte homeostasis and fate diversification in response to microbial infection. T cell-specific deletion of Lis1 resulted in depletion of the peripheral CD4(+) and CD8(+) T lymphocyte pool owing to a loss of homeostatic, cytokine-induced proliferation. In contrast, cognate Ag-triggered proliferation was much less affected, enabling Lis1-deficient CD8(+) T cells to differentiate into terminal effector cells in response to microbial infection. Strikingly, however, the specification of Lis1-deficient long-lived memory CD8(+) T lymphocytes was impaired due, in part, to an apparent failure to differentiate appropriately to IL-15. Taken together, these findings suggest that Lis1 plays an important role in T cell homeostasis and the generation of memory T lymphocytes.
authors.affiliation: Department of Medicine, University of California San Diego, La Jolla, CA 92093.
authors.forename: Soo M
authors.initials: SM
authors.lastname: Ngoi
authors.affiliation: Department of Medicine, University of California San Diego, La Jolla, CA 92093.
authors.forename: Justine M
authors.initials: JM
authors.lastname: Lopez
authors.affiliation: Department of Medicine, University of California San Diego, La Jolla, CA 92093 changj@ucsd.edu.
authors.forename: John T
authors.initials: JT
authors.lastname: Chang
mesh_terms: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000235:genetics / Q000276:immunology*; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology*; D002455:Cell Division; D006706:Homeostasis / Q000276:immunology; D007156:Immunologic Memory; D016130:Immunophenotyping; D019409:Interleukin-15 / Q000276:immunology; D015851:Interleukin-7 / Q000276:immunology; D008089:Listeria monocytogenes; D008088:Listeriosis / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction; D013950:Thymus Gland / Q000276:immunology
chemical_list: D019409:Interleukin-15; D015851:Interleukin-7; D008869:Microtubule-Associated Proteins; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; C513190:Pafah1b1 protein, mouse