title: In vivo behavior of peptide-specific T cells during mucosal tolerance induction: antigen introduced through the mucosa of the conjunctiva elicits prolonged antigen-specific T cell priming followed by anergy.
abstract: 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.
authors.affiliation: Department of Medicine, University of Kentucky Medical Center, Lexington, KY 40536, USA.
authors.forename: R M
authors.initials: RM
authors.lastname: Egan
authors.forename: C
authors.initials: C
authors.lastname: Yorkey
authors.forename: R
authors.initials: R
authors.lastname: Black
authors.forename: W K
authors.initials: WK
authors.lastname: Loh
authors.forename: J L
authors.initials: JL
authors.lastname: Stevens
authors.forename: E
authors.initials: E
authors.lastname: Storozynsky
authors.forename: E M
authors.initials: EM
authors.lastname: Lord
authors.forename: J G
authors.initials: JG
authors.lastname: Frelinger
authors.forename: J G
authors.initials: JG
authors.lastname: Woodward
mesh_terms: D000287:Administration, Topical; D000818:Animals; D000941:Antigens / Q000008:administration & dosage*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000637:transplantation*; D017635:Clonal Anergy; D002999:Clone Cells; D003228:Conjunctiva / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000008:administration & dosage* / Q000276:immunology; D007108:Immune Tolerance / Q000276:immunology*; D007117:Immunization, Secondary; D007279:Injections, Subcutaneous; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D009092:Mucous Membrane / Q000276:immunology; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D010455:Peptides / Q000008:administration & dosage / Q000276:immunology*; D013363:Submandibular Gland
chemical_list: D000941:Antigens; D018984:Epitopes, T-Lymphocyte; D010455:Peptides; D010047:Ovalbumin