Immune response to intragraft antigen in draining lymph nodes after corneal transplantation is mediated by interleukin-12

To examine the molecular basis of immunity generated to intragraft antigens and determine whether it differs between acceptor and rejector hosts, we u sed a novel in vitro system to assay the T cell response to a specific anti gen, ovalbumin (OVA), in the graft. OVA-containing corneas were orthotopica lly grafted into syngeneic or allogeneic hosts. Draining cervical lymph nod es (cLN) were assayed for OVA-specific T cell proliferation and cytokine pr oduction. In addition, cytokine production was assayed in cultures of antig en-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 im munity was evident well before any demonstrable alloresponse in the graft. In addition, cLN cells from mice that accepted their corneal allografts pro duced significantly less interferon-gamma (IFN-gamma) when stimulated in cu lture than cells harvested from cLN of rejector hosts. Moreover, APC isolat ed from cLN of acceptor hosts produced significantly lower levels of IL-12. These data suggest that the induction of immunity to corneal antigens in t he draining cLN occurs via an interleukin-12 (IL-12) and IFN-gamma -depende nt mechanism. Targeting this process may serve as an effective immunomodula tory strategy in corneal transplantation.