title: Type II collagen induces peripheral tolerance in BALB/c mice via the generation of CD8+ T regulatory cells.
abstract: Antigens introduced into the anterior chamber (AC) of the eye induce a potent form of antigen-specific peripheral immune tolerance termed AC-associated immune deviation (ACAID), which prevents inflammatory immune responses and is characterized by impaired delayed-type hypersensitivity (DTH) responses. Type-II collagen (CII) is a fibrillar protein expressed exclusively in cartilage tissues. Although of its clinical relevance to Rheumatoid arthritis, aging, and osteoarthritis, there have been no studies to date to test if CII has the ability to induce ACAID. We hypothesized that ACAID could be generated via AC injection of CII in BALB/c mice. Using a DTH assay, the hypothesis was supported and led to another hypothesis that CII is capable of inducing specific immune tolerance via CD8(+) T regulatory cells (Tregs). Thus, we performed functional local adoptive transfer (LAT) assays to examine the regulatory roles of spleen cells, T cells, and CD8(+) T cells in the specific immune regulation induced by CII injection into the AC. Results indicated that CII induced ACAID when injected into the AC. Spleen cells of mice injected with CII in the AC significantly suppressed DTH responses. The T cell compartment of the spleen was capable of expressing this suppression. CD8(+) Tregs could solely express this CII-driven suppression and even exerted more noticeable suppression than spleen cells or splenic T cells. This study suggests a crucial role for CD8(+) Tregs in mediating CII-driven ACAID-mediated immune tolerance. This could have therapeutic implications in Rheumatoid arthritis, aging, osteoarthritis, and other diseases in which CII is involved.
authors.affiliation: Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, Michigan, United States of America.
authors.forename: Shukkur M
authors.initials: SM
authors.lastname: Farooq
authors.forename: Hossam M
authors.initials: HM
authors.lastname: Ashour
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology*; D002356:Cartilage / Q000378:metabolism; D002469:Cell Separation; D024043:Collagen Type II / Q000378:metabolism*; D007108:Immune Tolerance; D051379:Mice; D008807:Mice, Inbred BALB C; D061166:Peripheral Tolerance; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000166:cytology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
chemical_list: D024043:Collagen Type II