Impaired development of Th2 cells in IL-13-deficient mice.
We report that Th2 cell cultures generated using T cells or splenocytes from IL-13-deficient mice produce significantly reduced levels of IL-4, IL-5, and IL-10 compared with wild-type. In contrast, IL-4 and IL-5 production by mast cells stimulated in vitro with PMA, ionomycin, or IgE cross-linking are unaffected. In vitro Th2 cell differentiation cannot be rescued by the addition of exogenous factors, but in vivo antigen challenge and administration of IL-13 can increase Th2-like cytokine responses as can infection with the parasitic nematode Nippostrongylus brasiliensis. IL-13-deficient mice also have lower basal levels of serum IgE and biased antigen-specific immunoglobulin responses. Thus, IL-13 is an important regulator of Th2 commitment and may therefore play a central role in atopy and infectious diseases.
MRC Laboratory of Molecular Biology, Cambridge, United Kingdom.
G J
GJ
McKenzie
C L
CL
Emson
S E
SE
Bell
S
S
Anderson
P
P
Fallon
G
G
Zurawski
R
R
Murray
R
R
Grencis
A N
AN
McKenzie
D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D002454:Cell Differentiation; D004351:Drug Resistance / Q000235:genetics; D018390:Gene Targeting / Q000379:methods; D007114:Immunization; D007073:Immunoglobulin E / Q000097:blood; D018793:Interleukin-13 / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D015847:Interleukin-4 / Q000096:biosynthesis; D015848:Interleukin-5 / Q000096:biosynthesis; D008407:Mast Cells / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016254:Mutagenesis, Insertional; D009349:Nematode Infections / Q000276:immunology; D009355:Neomycin / Q000494:pharmacology; D010735:Phosphoglycerate Kinase / Q000235:genetics; D017455:Receptors, IgE / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D013154:Spleen / Q000166:cytology; D018418:Th2 Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism
D018793:Interleukin-13; D015848:Interleukin-5; D017455:Receptors, IgE; D011994:Recombinant Proteins; D015847:Interleukin-4; D007073:Immunoglobulin E; D010735:Phosphoglycerate Kinase; D009355:Neomycin