Injection of soluble antigen into the anterior chamber of the eye induces expansion and functional unresponsiveness of antigen-specific CD8+ T cells.
The injection of soluble Ag into the anterior chamber (a.c.) of the eye induces systemic tolerance, termed a.c.-associated immune deviation (ACAID), characterized by Ag-specific inhibition of delayed-type hypersensitivity responses and a reduction in complement-fixing Abs. Recently, we have shown that CD8(+) CTL responses are also inhibited in ACAID. In this study, we have used an adoptive transfer approach to follow the fate of Ag-specific CD8(+) TCR transgenic (OT-I) T cells in vivo during the induction and expression of ACAID. C57BL/6 (B6) recipients of OT-I splenocytes that were injected with chicken OVA in the a.c. displayed reduced OVA-specific delayed-type hypersensitivity and CTL responses, compared with those of mice given OVA in the subconjunctiva or an irrelevant Ag human IgG in the a.c. OT-I T cells increased 9-fold in the submandibular lymph nodes and 3-fold in the spleen following an a.c. injection with OVA, indicating that expansion rather than deletion of Ag-specific CD8(+) T cells was induced by this treatment. OT-I T cells expanded equivalently upon administration of OVA in CFA to mice previously given OVA in the a.c. or subconjunctiva. However, the lytic activity attributed to OT-I T cells was reduced on a per-cell basis in mice previously given OVA in the a.c. We conclude that tolerance of CTL responses in mice given Ag via the a.c. results from unresponsiveness of Ag-specific CD8(+) T cells.
McKenna
Kyle C
KC
Departments of Ophthalmology and Pathology, Emory University School of Medicine, 1365 Clifton Road NE,, Atlanta, GA 30322, USA.
Xu
Yijun
Y
Kapp
Judith A
JA
D000818:Animals; D000867:Anterior Chamber; D000941:Antigens / Q000008:administration & dosage* / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D002455:Cell Division / Q000235:genetics / Q000276:immunology; D003228:Conjunctiva; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000008:administration & dosage / Q000276:immunology*; D005260:Female; D005620:Freund's Adjuvant / Q000008:administration & dosage; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007108:Immune Tolerance / Q000235:genetics / Q000276:immunology*; D007117:Immunization, Secondary; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000276:immunology; D007267:Injections; D018655:Lymphocyte Count; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000008:administration & dosage* / Q000276:immunology*; D012995:Solubility; D014407:Tumor Cells, Cultured
D000941:Antigens; D018984:Epitopes, T-Lymphocyte; D007074:Immunoglobulin G; D010047:Ovalbumin; D005620:Freund's Adjuvant