In vivo behavior of peptide-specific T cells during mucosal tolerance induction: Antigen introduced through the mucose of the conjunctiva elicits prolonged antigen-specific T cell priming followed by anergy

被引:60
作者
Egan, RM
Yorkey, C
Black, R
Loh, WK
Stevens, JL
Storozynsky, E
Lord, EM
Frelinger, JG
Woodward, JG [1 ]
机构
[1] Univ Kentucky, Med Ctr, Dept Microbiol & Immunol, Lexington, KY 40536 USA
[2] Univ Kentucky, Med Ctr, Dept Med, Lexington, KY 40536 USA
[3] Univ Kentucky, Med Ctr, Dept Ophthalmol, Lexington, KY 40536 USA
[4] Univ Rochester, Ctr Canc, Dept Microbiol & Immunol, Rochester, NY 14642 USA
关键词
D O I
10.4049/jimmunol.164.9.4543
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The mucosa of the conjunctiva is an important site of entry for environmental Ags as well as Ags emanating from the eye itself. However, very little is known about T cell recognition of Ag introduced through this important mucosal site. We have characterized the in vivo process of CD4 T cell recognition of Ag delivered via the conjunctival mucosa, Application of soluble OVA to the conjunctiva of BALB/c mice induced potent T cell tolerance, APC-presenting OVA peptide in vivo was only found in the submandibular lymph node and not in other lymph nodes, spleen, or nasal-associated lymphoid tissue. Similarly, in TCR transgenic DO11.10 adoptive transfer mice, OVA-specific CD4(+) T cell clonal expansion was only observed in the submandibular lymph node following conjunctival application of peptide. These experiments thus define a highly specific lymphatic drainage pathway from the conjunctiva, OVA-specific T cell clonal expansion peaked at day 3 following initiation of daily OVA administration and gradually declined during the 10-day treatment period, but remained elevated compared with nontreated adoptive transfer mice, During this period, the T cells expressed activation markers, and proliferated and secreted IL-2 in vitro in response to OVA stimulation. In contrast, these cells were unable to clonally expand in vivo, or proliferate in vitro following a subsequent OVA/CFA immunization. These results suggest that Ag applied to a mucosal site can be efficiently presented in a local draining lymph node, resulting in initial T cell priming and clonal expansion, followed by T cell anergy, The Journal of Immunology, 2000, 164: 4543-4550.
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页码:4543 / 4550
页数:8
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