CD8αα⁺ innate-type lymphocytes in the intestinal epithelium mediate mucosal immunity

Immunity. 2014 Sep 18;41(3):451-464. doi: 10.1016/j.immuni.2014.08.010. Epub 2014 Sep 11.

Abstract

Innate immune responses are critical for mucosal immunity. Here we describe an innate lymphocyte population, iCD8α cells, characterized by expression of CD8α homodimers. iCD8α cells exhibit innate functional characteristics such as the capacity to engulf and kill bacteria. Development of iCD8α cells depends on expression of interleukin-2 receptor γ chain (IL-2Rγc), IL-15, and the major histocompatibility complex (MHC) class Ib protein H2-T3, also known as the thymus leukemia antigen or TL. While lineage tracking experiments indicated that iCD8α cells have a lymphoid origin, their development was independent of the transcriptional suppressor Id2, suggesting that these cells do not belong to the family of innate lymphoid cells. Finally, we identified cells with a similar phenotype in humans, which were profoundly depleted in newborns with necrotizing enterocolitis. These findings suggest a critical role of iCD8α cells in immune responses associated with the intestinal epithelium.

Publication types

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

MeSH terms

  • Animals
  • Antigen Presentation / immunology*
  • CD8 Antigens / biosynthesis*
  • Citrobacter rodentium / immunology
  • Cytochalasin D / pharmacology
  • Enterocolitis, Necrotizing
  • Helicobacter pylori / immunology
  • Histocompatibility Antigens Class I / biosynthesis
  • Humans
  • Immunity, Mucosal / immunology*
  • Inhibitor of Differentiation Protein 2 / genetics
  • Interleukin Receptor Common gamma Subunit / biosynthesis
  • Interleukin-15 / biosynthesis
  • Interleukin-2 / biosynthesis
  • Interleukin-7 / biosynthesis
  • Intestinal Mucosa / cytology*
  • Intestinal Mucosa / immunology
  • Lymphocyte Activation / immunology
  • Lymphocytes / classification
  • Lymphocytes / cytology
  • Lymphocytes / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Phagocytosis / drug effects
  • Phagocytosis / immunology

Substances

  • CD8 Antigens
  • CD8 antigen, alpha chain
  • Histocompatibility Antigens Class I
  • Idb2 protein, mouse
  • Inhibitor of Differentiation Protein 2
  • Interleukin Receptor Common gamma Subunit
  • Interleukin-15
  • Interleukin-2
  • Interleukin-7
  • MICB antigen
  • Cytochalasin D