Mice with Th2-biased immune systems accept orthotopic corneal allografts placed in "high risk" eyes

CD4(+) T cells of the Th1 type play a central role in acute rejection of so lid tissue grafts, including orthotopic corneal allografts, Th1 cells, whic h mediate delayed hypersensitivity, are the polar opposites of CD4(+) Th2 c ells, and the latter cells cross-regulate Th1 cells through the unique patt ern of cytokines they secrete, As such, Th2 cells may have a useful role to play in preventing rejection of corneal allografts. To test this possibili ty, the immune systems of adult mice were biased toward Th2 responses by im munization with keyhole Limpet hemocyanin plus IFA, When immunized subseque ntly with either OVA or allogeneic corneal tissue, these mice acquired Ag-s pecific primed T cells of the Th2 type, More important, allogeneic corneas grafted into neovascularized eyes of Th2-biased mice experienced significan tly enhanced survival. To demonstrate that enhanced survival was promoted b y donor-specific Th2 cells, lymphoid cells from keyhole limpet hemocyanin-i mmune mice bearing healthy corneal allografts suppressed orthotopic corneal allograft rejection when adoptively transferred into naive, syngeneic reci pients. We conclude that acceptance of corneal allografts in neovascularize d mouse eyes can be significantly enhanced by biasing the recipient immune system toward Th2 responses.