Antiviral cytotoxic T lymphocyte responses for long term prognosis of corneal infection by cytomegalovirus in immunocompetent subjects

• Published in: Scientific reports Vol. 12; no. 1; pp. 5419 - 9
• Main Authors: Uotani, Ryu, Miyazaki, Dai, Shimizu, Yumiko, Ohtani, Fumie, Haruki, Tomoko, Sasaki, Shin-ichi, Koyama, Ayumi, Inoue, Yoshitsugu, Suzutani, Tatsuo
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 30.03.2022; Nature Publishing Group; Nature Portfolio
• Subjects: 631/326/596/2555; 692/420/254; 692/420/2780; 692/699/3161/3163; Antiviral Agents; Antiviral drugs; Cornea; Corneal transplantation; Cytomegalovirus; Cytomegalovirus - genetics; Cytotoxicity; Endothelial Cells; Glaucoma; Histocompatibility antigen HLA; Humanities and Social Sciences; Humans; IE1 protein; Immunocompetence; Lymphocytes; Lymphocytes T; multidisciplinary; Patients; Pp65 protein; Prognosis; Science; Science (multidisciplinary); T-Lymphocytes, Cytotoxic
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-022-09312-8

Ocular cytomegalovirus (CMV) infections in immunocompetent individuals are rare, but its activation can cause chronic and relapsing inflammation in anterior segment of the eye resulting in loss of corneal clarity and glaucoma. Fifty five patients with anterior segment CMV infection were assessed for their clinical characteristics, and CMV corneal endotheliitis was found to cause significant loss of corneal endothelial cells. The disease duration with recurrences was significantly correlated with the maximum intraocular level of CMV DNA. To examine why CMV is activated in healthy immunocompetent individuals and causing corneal endothelial cell damage, assays of cytotoxic T cells (CTLs) which directly target infected corneal endothelial cells were performed for 9 HLA-matched CMV corneal endotheliitis patients (HLA-A*2402). When the cell loss was analyzed for associations with CTL responses, CMV-induced endothelial cell damage was mitigated by pp65-specific CTL induction. The recurrence-free time was also prolonged by pp65-specific CTL induction (hazard ratio (HR): 0.93, P  = 0.01). In contrast, IE1-specific CTL was associated with endothelial cell damage and reduced the time for corneal transplantation (HR: 1.6, P  = 0.003) and glaucoma surgery (HR: 1.5, P  = 0.001). Collectively, induction of pp65-specific CTL was associated with improved visual prognosis. However, IE1-specific CTL without proper induction of pp65-specific CTL can cause pathological damage leading to the need of surgical interventions.