Corneal Graft Rejection In The Setting Of Previous Hsv-1 Infection

Abstract

Purpose: : Corneal grafts placed in patients with a history of ocular HSV-1 infection reject more quickly and often than grafts placed for non-inflammatory indications. The purpose of this study was to investigate the mechanism of corneal graft rejection in the high-risk setting of previous corneal HSV-1 infection.

Methods: : CD4 KO Balb/c mice were infected with HSV-1 via the cornea for 10 days prior to grafting with either WT Balb/c (syngraft) or C57BL/6 (allograft) corneal donor buttons. CD4 KO Balb/c hosts received 2x10⁶ naïve Balb/c CD4 T cells at time of grafting or not. Graft rejection was assessed by clinical biomicroscopy and scored based on corneal opacity. HSV-1 reactivation was assessed by clinical examination for recurrent periocular vesicular lesions and measurement of HSV-1 genome copy number in trigeminal ganglia of transplanted mice.

Results: : HSV-1 infection of CD4 KO Balb/c mice prior to allograft resulted in 100% rejection of grafts by 14 days post-transplant in mice that received CD4 T cell transfer. A portion of these mice demonstrated periocular vesicular lesions. Conversely, only ~10% of allografts rejected in HSV-1-infected mice that did not receive CD4 T cells. HSV-1 infection of CD4 KO Balb/c mice prior to syngeneic corneal transplantation resulted in ~30% graft rejection when CD4 T cells were transferred at the time of transplant. No rejection was seen in allografts placed onto non-infected CD4 KO Balb/c mice that received CD4 T cells. HSV-1 genome copy number was higher in trigeminal ganglia of HSV-infected CD4 KO Balb/c mice who rejected their allografts (i.e. received CD4 T cells) than those who did not (i.e. no CD4 T cells). No difference in HSV-1 genome copy number was observed in HSV-infected CD4 KO mice who received syngeneic grafts with or without CD4 T cell transfer.

Conclusions: : HSV-1 infection accelerates corneal graft rejection. CD 4 T cells are required for corneal graft rejection in the setting of previous HSV-1 infection. Allograft rejection in the setting of previous HSV-1 infection was associated with a higher number HSV-1 genome copies. Therefore, HSV-1 reactivation following corneal transplant likely contributes to the more rapid rejection.

Keywords: herpes simplex virus • keratitis • transplantation