A two-step process for cytokine production revealed by IL-4 dual-reporter mice.
To monitor IL-4 expression at the single-cell level, we generated mice with insertions of different reporter genes into both copies of the Il4 gene that permitted the simultaneous analysis of IL-4 transcripts via GFP and IL-4 protein secretion by use of huCD2. Innate and adaptive cells competent for IL-4 production were marked by GFP, while cells that presently or recently secreted IL-4 additionally displayed huCD2. After challenge with the strictly enteric helminth, Heligmosomoides polygyrus, GFP-positive innate and adaptive cells disseminated widely, but IL-4 secretion was predominantly mediated by CD4+ T cells in the intestines and draining lymphoid organs. IL-4-competent cells persisted in cured animals, and memory responses reflected rapid cytokine production at the site of rechallenge. These data reveal a two-step process for cytokine production: the first generating poised cells that disseminate systemically and the second inducing the rapid production of the cytokine in response to local stimulation.
Mohrs
Katja
K
Trudeau Institute, Saranac Lake, New York 12983, USA.
Wakil
Adil E
AE
Killeen
Nigel
N
Locksley
Richard M
RM
Mohrs
Markus
M
D000818:Animals; D000947:Antigens, Helminth; D018801:CD2 Antigens / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis*; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000235:genetics* / Q000276:immunology*; D015847:Interleukin-4 / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D008214:Lymphocytes / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D009351:Nematospiroides dubius / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
D000947:Antigens, Helminth; D018801:CD2 Antigens; D016207:Cytokines; D049452:Green Fluorescent Proteins; D015847:Interleukin-4