A distinct role for interleukin-13 in Th2-cell-mediated immune responses.
Immune responses elicited by allergic reactions and parasitic worm infections are characterised by the induction of T helper 2 (Th2) cells. These cells secrete cytokines such as interleukin-4 (IL-4), IL-5 and IL-13, which induce the production of immunoglobulin E (IgE) and eosinophils [1,2]. Previous studies using gastrointestinal nematodes to elucidate the role of Th2-cell-mediated immune responses have demonstrated a causal relationship between T cells and worm expulsion (reviewed in [3]). Although it has been proposed that IL-4 played a central role in these responses, recent studies demonstrated that IL-4-/- mice expel the parasitic gastrointestinal nematode Nippostrongylus brasiliensis normally [4], suggesting that another T-cell mediator is required for efficient worm clearance. Using IL-13-/- mice, we have demonstrated that, unlike wild-type and IL-4-/- mice, the IL-13-/- animals failed to clear N. brasiliensis infections efficiently, despite developing a robust Th2-like cytokine response to infection. Furthermore, treatment of the IL-13-/- mice with exogenous IL-13 resulted in a reduction in the numbers of worms recovered. The IL-13-/- animals also failed to generate the goblet cell hyperplasia that normally occurs coincident with worm expulsion. This observation may link IL-13 with the production of intestinal mucus which is believed to facilitate worm expulsion. These data support a unique role for IL-13 in Th2-cell-mediated immune responses and demonstrate that IL-13 and IL-4 are not redundant.
McKenzie
G J
GJ
MRC Laboratory of Molecular Biology, Cambridge, UK.
Bancroft
A
A
Grencis
R K
RK
McKenzie
A N
AN
D000818:Animals; D000909:Antibodies, Helminth / Q000302:isolation & purification; D002276:Carcinoid Tumor / Q000276:immunology; D016207:Cytokines / Q000302:isolation & purification; D007111:Immunity, Cellular; D007070:Immunoglobulin A / Q000302:isolation & purification; D007073:Immunoglobulin E / Q000302:isolation & purification; D007074:Immunoglobulin G / Q000302:isolation & purification; D018793:Interleukin-13 / Q000008:administration & dosage / Q000276:immunology* / Q000302:isolation & purification; D007411:Intestinal Diseases, Parasitic / Q000276:immunology / Q000469:parasitology; D007413:Intestinal Mucosa / Q000276:immunology; D008198:Lymph Nodes; D051379:Mice; D008810:Mice, Inbred C57BL; D009348:Nematoda / Q000276:immunology; D011994:Recombinant Proteins / Q000008:administration & dosage; D018418:Th2 Cells / Q000276:immunology* / Q000469:parasitology
D000909:Antibodies, Helminth; D016207:Cytokines; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D018793:Interleukin-13; D011994:Recombinant Proteins; D007073:Immunoglobulin E