Stimulation in vitro of lymphocytes for induction of uveoretinitis without any significant proliferation.

Abstract

Experimental autoimmune uveoretinitis can be adoptively transferred into naive recipients by lymphocytes from rats immunized with uveitogenic Ag, provided these cells are activated in vitro before being injected. The activation of sensitized lymphocytes, by the immunizing Ag, or by cross-reacting Ag, is usually accompanied by vigorous proliferation. We report, however, on a complete dissociation between the capacity of a peptide to generate uveitogenicity and to stimulate proliferation in cultured lymphocytes. This peptide, which occupies sequence 579-591 of the bovine interphotoreceptor retinoid-binding protein (IRBP), is one of the three "repeats" that exhibit partial sequence homologies with the immunodominant and highly immunogenic peptide, 1179-1191. Peptide 579-591 is nonimmunogenic and nonuveitogenic in Lewis rats and does not stimulate any significant proliferation in lymphocytes sensitized against whole IRBP, peptide 1179-1191, or another "repeat" peptide, 271-283, which is immunogenic and uveitogenic. In contrast, peptide 579-591 effectively generates uveitogenicity in the lymphocytes sensitized against these three Ag. Unlike 579-591, peptides 271-283 and 1179-1191 stimulated both proliferation and uveitogenicity in these sensitized lymphocytes. A different pattern of activities was observed with the other "repeat" peptide, 880-892. This peptide did not have any effect on the lymphocytes sensitized against IRBP, 271-283 or 1179-1191, but did stimulate both proliferation and uveitogenicity in lymphocytes sensitized against itself. The data suggest that 579-591 selectively stimulates a lymphocyte subset that is uveitogenic, but is incapable of mounting proliferative responses.