Evidence for an interleukin 4-inducible immunoglobulin E uptake and transport mechanism in the intestine.
Immunoglobulin (Ig) E is the principal Ig involved in immediate hypersensitivities and chronic allergic diseases such as asthma. Helminths are the most potent infectious agents known for their capacity to stimulate IgE production during the course of infection. In rats, the nematode Trichinella spiralis typically elicits a strong parasite-specific IgE response during infection, and this IgE antibody has been shown to be protective against the parasite in passive transfer experiments. The study reported here analyzed the fate of 125I-labeled myeloma IgE (1R162) in normal and T. spiralis-infected rats after intravenous injection. T. spiralis infection induced a capacity for specific binding to the gut wall of 125I-IgE rather than 125I-IgG1, as well as the transport of IgE, but not IgG1, into the gut lumen. Peak intestinal uptake and transport of 125I-IgE occurred during the first and second weeks after injection but was not elevated in the fourth week, that is, after intestinal adult worms had been expelled. Neither 125I-IgE uptake in the gut wall nor transport to the lumen could be ascribed to tissue damage or vascular leakage. Luminal transport occurred in the small intestine and not the liver, which only transports low molecular weight degraded 125I-IgE. Calculations based on the amount of intact IgE in the lumen suggest that, in a 24-h period, up to 20% of injected 125I-IgE can be transported to the gut lumen during the peak transport period, between 6 and 14 d after infection. The intestinal IgE binding and transport response can be adoptively transferred with T. spiralis immune CD4+ OX22- (CD45RC-) lymphocytes, which are protective, but not the nonprotective sister population CD4+ OX22+ (CD45RC+) of lymphocytes isolated simultaneously from thoracic duct lymph of infected rats. The intravenous infusion of recombinant rat interleukin 4 also elicited significant intestinal uptake of 125I-IgE. We also present evidence for the presence of CD23 on rat intraepithelial lymphocytes. These data provide evidence for a novel, inducible, intestine-specific IgE uptake and transport mechanism.
Ramaswamy
K
K
J.A. Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, New York 14853.
Hakimi
J
J
Bell
R G
RG
D000818:Animals; D001692:Biological Transport; D005260:Female; D006207:Half-Life; D007073:Immunoglobulin E / Q000032:analysis / Q000378:metabolism*; D016219:Immunotherapy, Adoptive; D015847:Interleukin-4 / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000378:metabolism*; D008297:Male; D008970:Molecular Weight; D011863:Radioimmunoassay; D051381:Rats; D017455:Receptors, IgE / Q000032:analysis; D013601:T-Lymphocytes / Q000276:immunology; D014018:Tissue Distribution; D014235:Trichinellosis / Q000378:metabolism
D017455:Receptors, IgE; D015847:Interleukin-4; D007073:Immunoglobulin E