Abstract
Purpose: :
To evaluate the effect of eye-specific DLN on the fate of corneal grafts in HSK recipients.
Methods: :
Cervical lymph node (LN) removal or sham procedure was performed one week before HSV-1 infection or one week before corneal graft procedure in HSK recipients. Corneal allografts (B6 --> BALB/c) or syngrafts (BALB/c) were performed using continuous suture. Graft rejection was assessed clinically by level of opacity; immunohistochemistry of grafted corneas was performed when the corneal opacity reached a score >2 or at the end of the observation period (60d post graft).
Results: :
DLN removal before the HSV-1 infection did not prevent the development of the HSK. However, some mice with bilateral cervical LN removal developed clinical signs of encephalitis. In HSK recipients with either DLN removal or sham procedure prior to allograft, 6% / 7% of recipients failed to reject the allograft (mean survival time (MST) 12d and 5d respectively). In contrast, 100% of HSK recipients with either DLN removal or sham procedure prior to syngraft rejected their graft (MST 14d and 4d respectively). Recipients with either LN or sham procedure prior to HSV-1 infection rejected 100% of allografts; however the severity and the speed of rejection was less vigorous (MST 18d and 12d respectively). Syngrafts in this group were accepted in a proportion of cases (40% and 80% respectively) with reduced survival rates of syngrafts in DLN removal group (MST 10d for rejected syngrafts). In addition, sham procedure-treated mice prior to HSV-1 infection and corneal syngraft experienced the highest reactivation rate of HSV (>50%), evidenced by vesicular eruption in the periocular adnexae. Immunohistology in all rejected corneal grafts showed massive infiltration of myeloid cells (F4/80/CD11b/Gr-1+ cells) together with substantial infiltration of lymphoid cells (CD4 and CD8+ T cells) in the host cornea as well as donor grafts. The presence of a thick retro-corneal membrane involving iris and donor graft was associated with all rejected corneal grafts.
Conclusions: :
The removal of the eye-draining LN had little influence on graft rejection in HSK and was associated with a fibrotic retrocorneal membrane.
Keywords: herpes simplex virus • transplantation • cornea: basic science