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Infection and Immunity, July 2004, p. 3803-3811, Vol. 72, No. 7
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.7.3803-3811.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Oral Tolerance in T Cells Is Accompanied by Induction of Effector Function in Lymphoid Organs after Systemic Immunization

Neetha Parameswaran, Devadoss John Samuvel,^, Ramesh Kumar, Sangeeta Thatai,^|| Vineeta Bal, Satyajit Rath, and Anna George^*

National Institute of Immunology, New Delhi 110067, India

Received 2 March 2004/ Accepted 5 April 2004

The physiological ramifications of oral tolerance remain poorly understood. We report here that mice fed ovalbumin (OVA) exhibit oral tolerance to subsequent systemic immunization with OVA in adjuvant, and yet they clear systemic infection with a recombinant OVA-expressing strain of Salmonella enterica serovar Typhimurium better than unfed mice do. Mice fed a sonicated extract of S. enterica serovar Typhimurium are also protected against systemic bacterial challenge, and the protection is Th1 mediated, as feeding enhances clearance in interleukin-4-null (IL-4^–/–) and IL-10^–/– mice but not in gamma interferon-null (IFN-^–/–) mice. When T-cell priming in vivo is tracked temporally in T-cell receptor-transgenic mice fed a single low dose of OVA, CD4 T-cell activation and expansion are restricted largely to mucosal lymphoid organs. However, T cells from spleens and peripheral lymph nodes of fed mice proliferate and secrete IFN- when restimulated with OVA in vitro, indicating the presence of primed T cells in systemic tissues following oral exposure to antigen. Nonetheless, oral tolerance can be observed in the fed mice as reduced recall responses following subsequent systemic immunization with OVA in adjuvant. Soluble OVA administered systemically has similar effects in vivo, and the "tolerance" seen in both cases can be partially reversed if the initial priming is made more immunogenic. Together, the results indicate that antigen exposure under poor adjuvantic conditions, whether oral or systemic, may lead to T-cell commitment to effector rather than proliferative capabilities, necessitating a reassessment of therapeutic modalities for induction of oral tolerance in allergic or autoimmune states.

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* Corresponding author. Mailing address: National Institute of Immunology, Aruna Asaf Ali Rd., New Delhi 110067, India. Phone: 91-11-26717121 or 91-11-26717125. Fax: 91-11-26162125. E-mail: anna-g{at}nii.res.in.

Editor: A. D. O'Brien

N.P. and D.J.S. contributed equally to this work.

Present address: Department of Physiology and Neuroscience, Medical University of South Carolina, Charleston, SC 29425.

Present address: Tan Tock Seng Hospital, Immunology Research Lab (Rheumatology, Allergy and Immunology), Singapore 308433, Singapore.

^|| Present address: LabIndia, New Delhi 10067, India.

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Infection and Immunity, July 2004, p. 3803-3811, Vol. 72, No. 7
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.7.3803-3811.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

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