Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0022568 (keratitis)
 5,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The requirement for T cell costimulation at sites of infection and inflammation is unresolved. Herpes stromal keratitis (HSK) is a CD4+ T cell-regulated inflammatory response to herpes simplex virus type 1 infection of the cornea. Our findings suggest that susceptibility to HSK is determined by the microenvironment of the infected cornea. The cornea is normally devoid of Langerhans cells (LC), but these APC are present in the surrounding conjunctiva, and migrate into the cornea following infection. The costimulatory molecule B7-2 was constitutively expressed on LC in conjunctiva, but B7-1 was not detectable until 3 days postinfection. LC were the only cells in the cornea that expressed B7-1 through 7 days postinfection. B7-1 was expressed on some, but not all, migrating LC, suggesting that LC migration and B7-1 expression can be independently regulated. The early LC migration and B7-1 expression was independent of T cells, but T cells were required for the massive accumulation of B7-1+ LC in the cornea at the onset of inflammation. Local inhibition of B7-1 function within the infected cornea prevented HSK. Locally blocking B7-2 function did not reduce HSK incidence, but markedly reduce HSK severity. This is the first direct demonstration that naturally expressed B7 is required within an inflammatory site.
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PMID:B7 costimulatory requirements of T cells at an inflammatory site. 959 Feb 54

Evidence suggests that Pseudomonas aeruginosa stromal keratitis and corneal perforation (susceptibility) is a CD4(+) T cell-regulated inflammatory response following experimental P. aeruginosa infection. This study examined the role of Langerhans cells (LC) and the B7/CD28 costimulatory pathway in P. aeruginosa-infected cornea and the contribution of costimulatory signaling by this pathway to disease pathology. After bacterial challenge, the number of LC infiltrating the central cornea was compared in susceptible C57BL/6 (B6) vs resistant (cornea heals) BALB/c mice. LC were more numerous at 1 and 6 days postinfection (p.i.), but were similar at 4 days p.i., in susceptible vs resistant mice. Mature, B7 positive-stained LC in the cornea and pseudomonas Ag-associated LC in draining cervical lymph nodes also were increased significantly p.i. in susceptible mice. To test the relevance of these data, B6 mice were treated systemically and subconjunctivally with neutralizing B7 (B7-1/B7-2) mAbs. Treatment decreased corneal disease severity and reduced significantly the number of B7-positive cells as well as the recruitment and activation of CD4(+) T cells in the cornea. IFN-gamma mRNA levels also were decreased significantly in the cornea and in draining cervical lymph nodes of mAb-treated mice. When CD28(-/-) animals were tested, they exhibited a less severe disease response (no corneal perforation) than wild-type B6 mice and had a significantly lower delayed-type hypersensitivity response to heat-killed pseudomonas Ag. These results support a critical role for B7/CD28 costimulation in susceptibility to P. aeruginosa ocular infection.
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PMID:B7/CD28 costimulation is critical in susceptibility to Pseudomonas aeruginosa corneal infection: a comparative study using monoclonal antibody blockade and CD28-deficient mice. 1114 12