Expression and function of the OX40/OX40L costimulatory pair during herpes stromal keratitis.
Herpes stromal keratitis (HSK) is an immunopathological disease regulated by Th1 CD4 T cells, which require APC and costimulation within the infected cornea to mediate disease. Recent studies suggest the OX40:OX40 ligand (OX40L) interaction enhances effector cell cytokine secretion at inflammatory sites. OX40(+) cells were detected in HSV-1-infected mouse corneas as early as 3 days postinfection (dpi), prior to the onset of HSK, and their frequency increased through 15 dpi, when all mice exhibited severe HSK. OX40L(+) cells were first detected at 7 dpi, coincident with the initiation of HSK. It is interesting that the OX40L(+) cells did not coexpress MHC Class II or the dendritic cell (DC) marker CD11c. Our findings demonstrate rapid infiltration of activated (OX40(+)) CD4(+) T cells into HSV-1-infected corneas and expression of OX40L on MHC Class II-negative cells but surprisingly, not on MHC Class II(+) CD11c(+) DC, which are present in the infected corneas and required for HSK. Moreover, neither local nor systemic treatment of mice with a blocking antibody to OX40L or with a blocking fusion protein altered the course of HSK significantly, possibly as a result of a lack of OX40L expression on functional APC.
Lepisto
Andrew J
AJ
Department of Ophthalmology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA.
Xu
Min
M
Yagita
Hideo
H
Weinberg
Andrew D
AD
Hendricks
Robert L
RL
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D003315:Cornea / Q000276:immunology* / Q000473:pathology / Q000821:virology; D005260:Female; D020869:Gene Expression Profiling; D018259:Herpesvirus 1, Human / Q000276:immunology; D007249:Inflammation; D016849:Keratitis, Herpetic / Q000276:immunology* / Q000821:virology; D008562:Membrane Glycoproteins / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D053278:OX40 Ligand; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D053262:Receptors, OX40 / Q000096:biosynthesis / Q000187:drug effects / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D048069:Tumor Necrosis Factors / Q000235:genetics / Q000502:physiology*
D000906:Antibodies; D008562:Membrane Glycoproteins; D053278:OX40 Ligand; D012333:RNA, Messenger; D053262:Receptors, OX40; C505717:Tnfrsf4 protein, mouse; C504586:Tnfsf4 protein, mouse; D048069:Tumor Necrosis Factors