NKG2A inhibits TH2 cell effector function in vitro

BMC Pulm Med. 2007 Oct 10:7:14. doi: 10.1186/1471-2466-7-14.

Abstract

Background: We previously reported that NKG2A, a key inhibitory ligand for HLA-E, is expressed on activated TH2 but not TH1 cells. Here we measured cytokine expression in human ex vivo TH2 cells upon activation with anti-CD3/28 and challenge with an NKG2A-specific agonist.

Methods: TH2 cells were purified from healthy volunteers and activated with anti-CD3/28 in the presence and absence of NKG2A-specific agonist. IL-4 was used as a marker of TH2 effector function and measured by flow cytometry.

Results: Activation of TH2 cells increased NKG2A positivity from (Mean +/- SE) 7.3 +/- 2.4% to 13.7 +/- 3.8%; (p = 0.03). The presence of NKG2A agonist did not significantly alter NKG2A expression, however, the percentage of activated TH2 cells expressing intracellular IL-4 decreased from 25.5 +/- 6.8% to 9.3 +/- 4.8% (p = 0.001).

Conclusion: We show that signalling through NKG2A suppresses TH2 effector function. This may provide a means to modulate Th1/Th2 balance in diseases where Th2 cytokines predominate.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Antibodies / pharmacology
  • CD28 Antigens / immunology
  • CD3 Complex / immunology
  • Cells, Cultured
  • Cytokines / metabolism*
  • Flow Cytometry
  • Humans
  • Interferon-gamma / metabolism
  • Interleukin-4 / antagonists & inhibitors
  • Interleukin-4 / metabolism
  • NK Cell Lectin-Like Receptor Subfamily C
  • Receptors, Immunologic / agonists
  • Receptors, Immunologic / metabolism*
  • Receptors, Natural Killer Cell
  • Signal Transduction / physiology*
  • Th2 Cells / metabolism*
  • Up-Regulation

Substances

  • Antibodies
  • CD28 Antigens
  • CD3 Complex
  • Cytokines
  • KLRC1 protein, human
  • NK Cell Lectin-Like Receptor Subfamily C
  • Receptors, Immunologic
  • Receptors, Natural Killer Cell
  • Interleukin-4
  • Interferon-gamma