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.