Orally tolerant CD4 T cells respond poorly to antigenic stimulation but strongly to direct stimulation of intracellular signaling pathways |
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Authors: | Kazumi Asai Satoshi Hachimura Terumasa Toraya Shuichi Kaminogawa |
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Institution: | (1) Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo 113–8657, Japan;(2) Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo 113–8657, Japan |
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Abstract: | The response of splenic CD4 T cells from ovalbumin (OVA)-specific T cell receptor (TCR) transgenic mice after long-term feeding
of a diet containing this antigen was examined. These CD4 T cells exhibited a decreased response to OVA peptide stimulation,
in terms of proliferation, interleukin-2 secretion, and CD40 ligand expression, compared to those from mice fed a control
diet lacking OVA, demonstrating that oral tolerance of T cells had been induced through oral intake of the antigen. We investigated
the intracellular signaling pathways, which were Ca/CN cascade and Ras/MAPK cascade, of these tolerant CD4 T cells using phorbol-12-myristate-13-acetate
(PMA) and ionomycin, which are known to directly stimulate these pathways. In contrast to the decreased response to TCR stimulation
by OVA peptide, it was shown that the response of splenic CD4 T cells to these reagents in the state of oral tolerance was
stronger. These results suggest that splenic CD4 T cells in the state of oral tolerance have an impairment in signaling, in
which signals are not transmitted from the TCR to downstream signaling pathways, and have impairments in the vicinity of TCR.
This revised version was published online in July 2006 with corrections to the Cover Date. |
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Keywords: | ionomy cin oral tolerance PMA signal transduction T cell |
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