Suppression of Th1 and Th17, but not Th2, responses in a CD8(+) T cell-mediated model of oral tolerance.
The role of CD8(+) T cells in oral tolerance remains unclear. To address this, we developed a model to induce CD8(+) Tregs by feeding the major histocompatibility complex class I immunodominant epitope of OVA, OVA((257-264)). OVA((257-264)) feeding induced tolerance similar to that observed in OVA protein-fed mice, capable of suppressing the production of Th1 and Th17 cytokines and inhibiting a Th1-driven delayed-type hypersensitivity response following immunization with whole OVA (wOVA) protein. OVA((257-264)) peptide-induced suppression could be transferred to naive mice with CD8(+) cells, but not CD8-depleted cells, isolated from mesenteric lymph nodes of peptide-fed mice. Interestingly, while capable of inhibiting Th1 and Th17 responses, OVA((257-264)) feeding could not suppress any feature of a Th2 inflammatory response, though OVA protein feeding could, suggesting that these cells function through a different mechanism than their CD4(+) counterparts generated in response to feeding with wOVA. Thus, CD8(+) T cells are functionally capable of mediating tolerance to Th1 and Th17 responses.
Arnaboldi
P M
PM
Immunology Institute, The Mount Sinai School of Medicine, New York, New York, USA.
Roth-Walter
F
F
Mayer
L
L
D000281:Administration, Intranasal; D000284:Administration, Oral; D019264:Adoptive Transfer; D000542:Alveolitis, Extrinsic Allergic / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D000818:Animals; D000941:Antigens / Q000008:administration & dosage* / Q000276:immunology / Q000633:toxicity; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D003888:Desensitization, Immunologic / Q000379:methods*; D004431:Ear, External / Q000276:immunology / Q000473:pathology; D004487:Edema / Q000209:etiology / Q000276:immunology / Q000473:pathology; D007108:Immune Tolerance / Q000276:immunology*; D007114:Immunization; D016056:Immunodominant Epitopes / Q000008:administration & dosage* / Q000276:immunology / Q000633:toxicity; D007271:Injections, Intradermal; D008211:Lymphocyte Cooperation; D051379:Mice; D008810:Mice, Inbred C57BL; D018448:Models, Immunological; D010047:Ovalbumin / Q000008:administration & dosage* / Q000276:immunology / Q000633:toxicity; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology / Q000633:toxicity; D016176:T-Lymphocyte Subsets / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D000941:Antigens; D016056:Immunodominant Epitopes; C110366:OVA-8; D010446:Peptide Fragments; D010047:Ovalbumin