International Immunology, Vol. 11, No. 12, 1907-1916,
December 1999
© 1999 Japanese Society for Immunology
T cells regulate mucosally induced tolerance in a dose-dependent fashion
1 Departments of Oral Biology,
2 Microbiology,
4 Medicine and
5 Pediatrics, Immunobiology Vaccine Center, and the
6 Howard Hughes Medical Institute, University of Alabama at Birmingham, Medical Center, Birmingham, AL 35294, USA
7 Center for Cancer Research, Department of Biology, Howard Hughes Medical Institute and Massachusetts Institute of Technology, Cambridge, MA 02139, USA
3 Department of Mucosal Immunology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565, Japan
Correspondence to: K. Fujihashi, Department of Oral Biology, Immunobiology Vaccine Center, University of Alabama at Birmingham, Medical Center, BBRB 761, Birmingham, AL 35294-2170, USA
We used 
TCR-deficient (TCR–/–) mice to examine the role of T cells for induction of mucosal responses and systemic tolerance to high versus low doses of oral antigen. When either TCR–/– or TCR+/+ mice were immunized orally with a high dose of ovalbumin (OVA) prior to parenteral challenge, systemic IgG and IgE antibody responses were markedly reduced in both types of mice, while mucosal IgA responses were reduced only in the TCR–/– mice. Reduced T cell proliferative responses and delayed-type hypersensitivity were seen in TCR–/– and TCR+/+ mice given the high dose of OVA. Antigen-induced Th1 and Th2 cytokine production by splenic CD4+ T cells was severely inhibited in orally tolerized TCR–/– and TCR+/+ mice. In contrast, while oral tolerance associated with increased levels of IL-10 synthesis was induced by a low dose of OVA in TCR+/+ mice, the TCR–/– mice were not tolerized and failed to produce IL-10. Our findings indicate that T cells play a significant immunoregulatory role in IL-10-mediated, low-dose oral tolerance induction, but are not essential participants in the induction of systemic tolerance to orally introduced antigens given in larger doses.
Keywords: CD4+ T cells, knockout mice, T cells, oral antigens, tolerance
Transmitting editor: S.-i. Nishikawa
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