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Infection and Immunity, January 2000, p. 46-53, Vol. 68, No. 1
0019-9567/0/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Igh-6minus /minus (B-Cell-Deficient) Mice Fail To Mount Solid Acquired Resistance to Oral Challenge with Virulent Salmonella enterica Serovar Typhimurium and Show Impaired Th1 T-Cell Responses to Salmonella Antigens

Pietro Mastroeni,1,2,* C. Simmons,2 R. Fowler,2 C. E. Hormaeche,3 and G. Dougan2

Centre for Veterinary Science, University of Cambridge, Cambridge CB3 OES,1 Department of Biochemistry, Imperial College of Science, Technology and Medicine, South Kensington, London SW7 2AZ,2 and School of Microbiological, Immunological and Virological Sciences, The Medical School, University of Newcastle, Newcastle upon Tyne NE2 4HH,3 United Kingdom

Received 21 June 1999/Returned for modification 19 August 1999/Accepted 20 October 1999

In the present study we evaluated the role of B cells in acquired immunity to Salmonella infection by using gene-targeted B-cell-deficient innately susceptible mice on a C57BL/6 background (Igh-6-/-). Igh-6-/- mice immunized with a live, attenuated aroA Salmonella enterica serovar Typhimurium vaccine strain showed impaired long-term acquired resistance against the virulent serovar Typhimurium strain C5. Igh-6-/- mice were able to control a primary infection and to clear the inoculum from the reticuloendothelial system. However, Igh-6-/- mice, unlike Igh-6+/+ C57BL/6 controls, did not survive an oral challenge with strain C5 at 4 months after vaccination. Transfer of immune serum did not restore resistance in Igh-6-/- mice. Total splenocytes and purified CD4+ T cells obtained from Igh-6-/- mice 4 months after vaccination showed reduced ability to release Th1-type cytokines (interleukin 2 and gamma interferon) upon in vitro restimulation with serovar Typhimurium soluble cell extracts compared to cells obtained from Igh-6+/+ C57BL/6 control mice. Therefore, the impaired resistance to oral challenge with virulent serovar Typhimurium observed in B-cell-deficient mice, which cannot be restored by passive transfer of Salmonella-immune serum, may be in part due to a reduced serovar Typhimurium-specific T-cell response following primary immunization.

* Corresponding author. Mailing address: Centre for Veterinary Science, University of Cambridge, Madingley Road, Cambridge CB3 OES, United Kingdom. Phone: 44 1223 766233. Fax: 44 1223 337610. E-mail: pm274{at}cam.ac.uk.

Infection and Immunity, January 2000, p. 46-53, Vol. 68, No. 1
0019-9567/0/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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