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Infection and Immunity, November 2002, p. 6215-6222, Vol. 70, No. 11
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.11.6215-6222.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Induction of Cytolytic Anti-Gal Antibodies in {alpha}-1,3-Galactosyltransferase Gene Knockout Mice by Oral Inoculation with Escherichia coli O86:B7 Bacteria

Karla J. Posekany,1 H. Keith Pittman,2 John F. Bradfield,3 Carl E. Haisch,1,2 and Kathryn M. Verbanac1,2*

Department of Microbiology and Immunology,1 Department of Surgery,2 Department of Comparative Medicine, The Brody School of Medicine at East Carolina University, Greenville, North Carolina 278583

Received 5 April 2002/ Returned for modification 24 June 2002/ Accepted 23 July 2002

Naturally occurring antibodies against [Gal {alpha}-1,3-Gal] structures (anti-Gal antibodies) are the primary effectors of human hyperacute rejection (HAR) of nonhuman tissue. Unlike most mammals, humans lack a functional {alpha}-1,3-galactosyltransferase (GalT) gene and produce abundant anti-Gal antibodies, putatively in response to GalT+ enteric bacteria. GalT knockout (KO) mice have been generated as a small animal model of HAR but inconsistently express anti-Gal antibodies. We hypothesized that enteric exposure of GalT KO mice to live GalT+ bacteria would produce cytolytic anti-Gal antibodies. Naive mice lacking anti-Gal antibodies were orally immunized with 1010 live GalT+ Escherichia coli O86:B7 bacteria and assayed for anti-Gal antibody titer, isotype, and cytolytic activity. Fecal samples were tested for E. coli O86:B7 prior to and after inoculation. In two separate experiments, 77 to 100% (n = 31) of mice developed serum anti-Gal immunoglobulin G (IgG; titer, 1:5 to 1:80) and/or anti-Gal IgM antibodies (titer, 1:5 to 1:1,280) 14 days postinoculation. Induced anti-Gal antibodies caused complement-mediated cytolysis of GalT+ target cells, with extensive cytolysis observed consistently at serum IgM titers of >=1:320. Absorption with synthetic [Gal {alpha}-1,3-Gal] inhibited both antibody binding and cytolysis. E. coli O86:B7 was recovered from stool samples from 83 to 94% of inoculated mice but not from naive mice, thus confirming enteric exposure. These findings demonstrate that oral inoculation with E. coli O86:B7 is a novel and effective method to induce cytolytic anti-Gal antibodies in GalT KO mice and support the premise that enteric exposure to GalT+ bacteria induces anti-Gal antibodies in humans. These studies also suggest a role for GalT KO mice in elucidating anti-Gal responses in microbial immunity.

* Corresponding author. Mailing address: Department of Surgery, The Brody School of Medicine at East Carolina University, Greenville, NC 27858-4354. Phone: (252) 816-3689. Fax: (252) 816-0032. E-mail: verbanack{at}mail.ecu.edu.

Editor: B. B. Finlay

Infection and Immunity, November 2002, p. 6215-6222, Vol. 70, No. 11
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.11.6215-6222.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • POSEKANY, K. J., WILEY, J. E., GAGNON, G. A. (2009). A Novel Method to Display [gal {alpha}1, 3 gal] Antigens on Human Leukemic Cells for Preparation of Anti-leukemia Vaccines. Anticancer Res 29: 2387-2392 [Abstract] [Full Text]  
  • Rossi, G. R., Mautino, M. R., Unfer, R. C., Seregina, T. M., Vahanian, N., Link, C. J. (2005). Effective Treatment of Preexisting Melanoma with Whole Cell Vaccines Expressing {alpha}(1,3)-Galactosyl Epitopes. Cancer Res. 65: 10555-10561 [Abstract] [Full Text]  


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