Immunological disruption of antiangiogenic signals by recruited allospecific T cells leads to corneal allograft rejection

Corneal transplantation is the most common solid organ transplantation. The immunologically privileged nature of the cornea results in high success rates. However, T cell-mediated rejection is the most common cause of corneal graft failure. Using antiangiogenesis treatment to prevent corneal neovascularization, which revokes immune privilege, prevents corneal allograft rejection. Endostatin is an antiangiogenic factor that maintains corneal avascularity. In this study, we directly test the role of antiangiogenic and immunological signals in corneal allograft survival, specifically the potential correlation of endostatin production and T cell recruitment. We report that 75% of the corneal allografts of BALB/c mice rejected after postoperative day (POD) 20, whereas all syngeneic grafts survived through POD60. This correlates with endogenous endostatin, which increased and remained high in syngeneic grafts but decreased after POD10 in allografts. Immunostaining demonstrated that early recruitment of allospecific T cells into allografts around POD10 correlated with decreased endostatin production. In Rag(-/-) mice, both allogeneic and syngeneic corneal grafts survived; endostatin remained high throughout. However, after T cell transfer, the allografts eventually rejected, and endostatin decreased. Furthermore, exogenous endostatin treatment delayed allograft rejection and promoted survival secondary to angiogenesis inhibition. Our results suggest that endostatin plays an important role in corneal allograft survival by inhibiting neovascularization and that early recruitment of allospecific T cells into the grafts promotes destruction of endostatin-producing cells, resulting in corneal neovascularization, massive infiltration of effector T cells, and ultimately graft rejection. Therefore, combined antiangiogenesis and immune suppression will be more effective in maintaining corneal allograft survival.     

Cut-off Scores of a Brief Neuropsychological Battery (NBACE) for Spanish Individual Adults Older than 44 Years Old

The neuropsychological battery used in Fundació ACE (NBACE) is a relatively brief, and easy to administer, test battery that was designed to detect cognitive impairment in the adulthood. The NBACE includes measures of cognitive information processing speed, orientation, attention, verbal learning and memory, language, visuoperception, praxis and executive functions. The aim of the present study was to establish the cut-off scores for impairment for different levels of age and education that could be useful in the cognitive assessment of Spanish subjects who are at risk for cognitive impairment, especially dementia. Data from 1018 patients with a mild dementia syndrome, and 512 cognitively healthy subjects, older than 44 years, from the Memory Clinic of Fundació ACE (Barcelona, Spain) were analyzed. In the whole sample, cut-off scores and sensitivity/specificity values were calculated for six conditions after combining 3 age ranges (44 to 64; 65 to 74; and older than 74 years old) by 2 educational levels (until Elementary school; and more than Elementary school). Moreover, general cut-offs are reported for Catalan and Spanish speakers. The results showed that most of NBACE tests reached good sensitivity and specificity values, except for Ideomotor praxis, Repetition and Verbal Comprehension tests, which had a ceiling effect. Word List Learning from the Wechsler Memory Scale-III and Semantic Verbal Fluency were the most useful tests to discriminate between cognitively healthy and demented subjects. The NBACE has been shown to be a useful tool able to detect cognitive impairment, especially dementia, in older than 44 years Spanish persons.