Amniotic membrane transplantation induces apoptosis in T lymphocytes in murine corneas with experimental herpetic stromal keratitis

¹ Ophtha-Lab, Department of Ophthalmology, Muenster, Germany
² Department of Ophthalmology, University of Duisburg-Essen, Essen, Germany

^* To whom correspondence should be addressed. E-mail: Dirk.Bauer{at}uveitis-zentrum.de.

	Abstract

Purpose: To investigate the effect of human amniotic membrane transplantation (AMT) on T-cell immune response in murine corneas with herpetic stromal keratitis (HSK). Methods: HSV-1-infected BALB/c-mice with necrotizing HSK were treated with AMT. CD3+ cell apoptosis was determined in treated corneas and in vitro by flow cytometric analysis using the annexin V/7-AAD system. The effect of interleukin (IL)-2, cyclosporine A, rapamycin, or Fas on T-cell survival was measured. Activation phenotype was measured by 3H-thymidine uptake and flow cytometry (CD25, CD69, MHC-II). Cytokine/chemokine secretion from AM-treated corneas or draining lymph node (DLN) cells was measured. The immune modulating capacity of long-term AMT treatment and adoptive transfer of AM-treated splenocytes was tested . Results: After AMT, HSK and corneal inflammatory cell infiltration improved, and T-lymphocyte apoptosis occurred. T-cell apoptosis was also induced in vitro, independently of rIL-2, cyclosporine A, rapamycin, or Fas. AMT-treated corneas and cultured lymphocytes had a reduced IL-2, IL-10, IL-12, CRG-2, and CCL-2 content. Long-term AMT treatment decreased the proliferative response and Th1 cytokines in DLN cells. The improvement in HSK did not persist. DTH or HSV-1-specific cytotoxicity was not altered. Conclusions: The results suggest that murine HSK improves after AMT via reduced local Th immune responses by inducing apoptosis in T lymphocytes, independently of passive apoptosis or activation-induced cell death. AM also reduces local Th cytokine and chemokine levels, but does not result in immune deviation. The immunological memory against HSV-1 is not affected by AMT; nor is long-term protection or tolerance induced.

Key Words: herpes simplex keratitis, anti-inflammatory agents, apoptosis

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