Immune Response to Intragraft Antigen in Draining Lymph Nodes After Corneal Transplantation Is Mediated by Interleukin-12

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Abstract
To examine the molecular basis of immunity generated to intragraft antigens and determine whether it differs between acceptor and rejector hosts, we used a novel in vitro system to assay the T cell response to a specific antigen, ovalbumin (OVA), in the graft. OVA-containing corneas were orthotopically grafted into syngeneic or allogeneic hosts. Draining cervical lymph nodes (cLN) were assayed for OVA-specific T cell proliferation and cytokine production. In addition, cytokine production was assayed in cultures of antigen-presented cells (APC) isolated from cLN cultured with OVA-specific DO11.10 T cells and OVA. OVA-specific immunity was detected only in the draining cLN of mice following allogeneic, but not syngeneic, grafting, and this immunity was evident well before any demonstrable alloresponse in the graft. In addition, cLN cells from mice that accepted their corneal allografts produced significantly less interferon-γ (IFN-γ) when stimulated in culture than cells harvested from cLN of rejector hosts. Moreover, APC isolated from cLN of acceptor hosts produced significantly lower levels of IL-12. These data suggest that the induction of immunity to corneal antigens in the draining cLN occurs via an interleukin-12 (IL-12) and IFN-γ-dependent mechanism. Targeting this process may serve as an effective immunomodulatory strategy in corneal transplantation.