title: Blocking 4-1BB/4-1BB ligand interactions prevents herpetic stromal keratitis.
abstract: Herpetic stromal keratitis (HSK) is a chronic inflammatory process in corneal stroma that results from recurrent HSV type 1 infection. We used the murine model of HSK to demonstrate the importance of the interaction between an inducible T cell costimulatory receptor, 4-1BB, and its ligand, 4-1BB ligand (4-1BBL), in the development of this disease. In BALB/c mice, HSK ordinarily induced by infection with the RE strain of herpes was prevented by blocking 4-1BB/4-1BBL interaction, either by deleting 4-1BB (in mutant 4-1BB(-/-) mice) or by introducing mAbs against 4-1BBL. The majority of T cells infiltrating the infected corneas were 4-1BB(+) activated effector cells that expressed cell surface markers CD44, CD25, and/or CD62L, as well as chemokine receptors CCR1, CCR2, and CCR5, and a limited number of TCR Vbeta chains (Vbeta8.1/8.2, Vbeta8.3, Vbeta10b, and Vbeta5.1/5.2, in order of abundance). Analysis of cell surface phenotypes showed that the failure to develop HSK in the 4-1BB(-/-) mice was associated with a reduced expression of CD62L at the time of T cell migration into the corneal stroma.
authors.affiliation: Immunomodulation Research Center, University of Ulsan, Ulsan, Korea.
authors.forename: Su K
authors.initials: SK
authors.lastname: Seo
authors.forename: Hye Y
authors.initials: HY
authors.lastname: Park
authors.forename: Jae H
authors.initials: JH
authors.lastname: Choi
authors.forename: Won Y
authors.initials: WY
authors.lastname: Kim
authors.forename: Young H
authors.initials: YH
authors.lastname: Kim
authors.forename: Hyo W
authors.initials: HW
authors.lastname: Jung
authors.forename: Byungsuk
authors.initials: B
authors.lastname: Kwon
authors.forename: Hyeon W
authors.initials: HW
authors.lastname: Lee
authors.forename: Byoung S
authors.initials: BS
authors.lastname: Kwon
mesh_terms: D053330:4-1BB Ligand; D000818:Animals; D015703:Antigens, CD; D017209:Apoptosis / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D018925:Chemokines / Q000096:biosynthesis; D003315:Cornea / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000096:biosynthesis; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology; D017353:Gene Deletion; D018259:Herpesvirus 1, Human / Q000276:immunology; D016130:Immunophenotyping; D016849:Keratitis, Herpetic / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control* / Q000821:virology; D019041:L-Selectin / Q000096:biosynthesis; D008024:Ligands; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D017475:Receptors, Nerve Growth Factor / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000172:deficiency / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000172:deficiency / Q000378:metabolism*; D017154:Stromal Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism / Q000821:virology; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000378:metabolism*
chemical_list: D053330:4-1BB Ligand; D015703:Antigens, CD; D018925:Chemokines; D016207:Cytokines; D008024:Ligands; D017475:Receptors, Nerve Growth Factor; D018124:Receptors, Tumor Necrosis Factor; C505714:TNFRSF9 protein, human; C505974:TNFSF9 protein, human; C505715:Tnfrsf9 protein, mouse; C505975:Tnfsf9 protein, mouse; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9; D014409:Tumor Necrosis Factor-alpha; D019041:L-Selectin