NKG2A inhibits TH2 cell effector function in vitro.
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).


CONCLUSIONS
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.
Freishtat
Robert J
RJ
Division of Emergency Medicine, Children's National Medical Center, Washington, DC, USA. rfreishtat@cnmcresearch.org
Mojgani
Bahar
B
Nazemzadeh
Maryam
M
Nagaraju
Kanneboyina
K
Hoffman
Eric P
EP
D000906:Antibodies / Q000494:pharmacology; D018106:CD28 Antigens / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D005434:Flow Cytometry; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000037:antagonists & inhibitors / Q000378:metabolism; D055654:NK Cell Lectin-Like Receptor Subfamily C; D011971:Receptors, Immunologic / Q000819:agonists / Q000378:metabolism*; D055607:Receptors, Natural Killer Cell; D015398:Signal Transduction / Q000502:physiology*; D018418:Th2 Cells / Q000378:metabolism*; D015854:Up-Regulation
D000906:Antibodies; D018106:CD28 Antigens; D017252:CD3 Complex; D016207:Cytokines; C527054:KLRC1 protein, human; D055654:NK Cell Lectin-Like Receptor Subfamily C; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell; D015847:Interleukin-4; D007371:Interferon-gamma