INTRAOCULAR INJECTION OF CLASS II-RESTRICTED PEPTIDE INDUCES AN UNEXPECTED POPULATION OF CD8 REGULATORY CELLS

Intraocular injection of exogenous protein induces an Ag-specific impa irment of systemic delayed hypersensitivity (DH), termed anterior cham ber associated immune deviation (ACAID). The ACAID-inducing signal is carried by blood-borne cells from the eye to the spleen and can also b e generated in vitro by incubating APCs with Ag plus TGF-beta. Paradox ically, class I-restricted CD8 regulatory cells are induced in the spl eens of mice with ACAID, and previous studies suggest that CD8 cells a re important, and even necessary, for the expression of ACAID. To expl ore this issue further, we asked whether ACAID could be induced with a class II-restricted peptide, and if so, what type of regulatory cells are generated, An intraocular, but not an i.v., injection of OVA (323 -339) peptide resulted in impairment of native OVA-specific DH in both naive and previously sensitized mice, Furthermore, i.v. injection of APCs pretreated with TGF-beta plus OVA peptide also prevented native O VA-specific DH. Surprisingly, both CD8(+) and CD4(+) spleen cells capa ble of impairing expression of DH were induced by either intraocular i njection of peptide or i.v. injection of APCs pretreated with peptide plus TGF-beta. In summary, ACAID can be induced by a class II-restrict ed peptide and is accompanied by the generation of two unusual populat ions of cells: 1) CD8(+) regulatory cells unexpectedly induced by clas s II-restricted peptide; and 2) a novel population of CD4 regulatory c ells induced by peptide, but not native protein. Potential mechanisms involved in the processing and presentation of exogenous protein in th e ACAID model are discussed in light of the present data.