A shared gene-expression signature in innate-like lymphocytes

Authors

  • Tetsuya Yamagata,

    1. Department of Hematology, Dokkyo Medical School, Tochigi, Japan
    Search for more papers by this author
  • Christophe Benoist,

    1. Department of Medicine, Section on Immunology and Immunogenetics, Joslin Diabetes Center, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
    Search for more papers by this author
  • Diane Mathis

    Corresponding author
    1. Department of Medicine, Section on Immunology and Immunogenetics, Joslin Diabetes Center, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
    Search for more papers by this author

* Diane Mathis
Department of Medicine
Section on Immunology and Immunogenetics
Joslin Diabetes Center
Brigham and Women's Hospital
Harvard Medical School
One Joslin Place
Boston, MA 02215
USA
Tel.: +1 617 264 2745
Fax: +1 617 264 2744
E-mail: cbdm@joslin.harvard.edu

Abstract

Summary:  Innate and adaptive immunities are the two major arms of the immune system, which rely on distinct cell types. These cells can be distinguished not only by the source of diversity for non-self recognition, of germline or somatic origin, but also by their localization and the pattern and rates of response after encounter of antigenic triggers. In addition, subsets of lymphocytes exist whose receptors require rearrangement but result in semi-invariant structures with a high degree of self-specificity. We hypothesized that these innate-like lymphocytes might share a common gene transcription signature that relates them to classic members of the innate immune system. This relationship was first observed in agonist-induced CD8αα T cells in fetal/neonatal thymus. We then asked whether this notion could be extended to other innate-like lymphocytes, by comparison of gene expression profiles of innate-like lymphocytes and closely paired adaptive system counterparts (NKT versus CD4T, CD8ααT versus CD8αβT, and B1 versus B2). A statistically significant ‘innate signature’ indeed was distilled. Particularly intriguing was the high representation of interferon-inducible guanosine triphophatases crucial for resistance against intracellular pathogens and of small G proteins involved in intracellular vacuole maturation and trafficking. Overall, this combined expression pattern can be designated as an innate signature among lymphocytes.

Ancillary