Asymmetric T lymphocyte division in the initiation of adaptive immune responses

Science. 2007 Mar 23;315(5819):1687-91. doi: 10.1126/science.1139393. Epub 2007 Mar 1.

Abstract

A hallmark of mammalian immunity is the heterogeneity of cell fate that exists among pathogen-experienced lymphocytes. We show that a dividing T lymphocyte initially responding to a microbe exhibits unequal partitioning of proteins that mediate signaling, cell fate specification, and asymmetric cell division. Asymmetric segregation of determinants appears to be coordinated by prolonged interaction between the T cell and its antigen-presenting cell before division. Additionally, the first two daughter T cells displayed phenotypic and functional indicators of being differentially fated toward effector and memory lineages. These results suggest a mechanism by which a single lymphocyte can apportion diverse cell fates necessary for adaptive immunity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • Antigen Presentation
  • Antigens, CD / analysis
  • CD8 Antigens / analysis
  • CD8-Positive T-Lymphocytes / cytology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Differentiation
  • Cell Division*
  • Cell Lineage
  • Cell Polarity
  • Dendritic Cells / immunology
  • Immunologic Memory*
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Listeria monocytogenes / immunology
  • Listeriosis / immunology
  • Lymphocyte Activation
  • Membrane Proteins / analysis
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Mitosis
  • Nerve Tissue Proteins / analysis
  • Protein Kinase C / metabolism
  • Receptors, Antigen, T-Cell / immunology
  • Receptors, Interferon / analysis
  • Signal Transduction
  • T-Lymphocyte Subsets / cytology*
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocytes, Helper-Inducer / immunology

Substances

  • Antigens, CD
  • CD8 Antigens
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Numb protein, mouse
  • Receptors, Antigen, T-Cell
  • Receptors, Interferon
  • scribble protein, mouse
  • interferon gamma receptor
  • protein kinase C zeta
  • Protein Kinase C