A CD25+ cell suppresses the proliferation of peanut-specific CD8+ T cells from nonallergic individuals.

CD8+ T cells are associated with pathologic immune responses to food as seen in eosinophilic esophagitis, celiac disease, and - as we have recently reported – with IgE mediated peanut allergy. Little is known about the behavior of food-specific CD8+ T cells in healthy people. We previously identified a peanut peptide recognized by CD8+ T cells in the context of HLA-A*02:01 from a peanut allergic individual. We generated HLA-A*02:01 tetramers with this peanut peptide and then used tetramer enrichment to isolate peanut specific CD8+ T cell from nonallergic, HLA-A*02:01+ blood donors. Peanut specific CD8+ T cells from nonallergic individuals were stimulated with peptide, and after 1 week, the expansion of peanut specific CD8+ T cells was measured by enumerating peanut tetramer+ cells by flow cytometry. Peanut specific CD8+ T cells were detectable in the blood of nonallergic individuals at frequencies consistent with other antigen specific CD8+ T cells. When stimulated with peptide and anti-CD28 antibody in the presence of autologous PBMCs, peanut specific CD8+ T cells did not expand in comparison to naive CD8+ T cells specific for foreign epitopes. The proliferation block observed in peanut specific CD8+ T cells can be released by depleting of CD25+ cells from the autologous feeder PBMCs. Our preliminary data indicate that peanut-specific CD8+ T cells are not clonally deleted by the immune system to maintain tolerance but instead are regulated by CD25+ cells, suggesting that active suppression contributes to the maintenance of CD8+ T cell tolerance to food antigens in nonallergic individuals.