Human Peyer's patch T cells are sensitized to dietary antigen and display a Th cell type 1 cytokine profile

Animal studies have demonstrated that feeding Ags induces regulatory (Th2, Th3) cells in Peyer's patches (PP), which migrate to the periphery and prod uce immunomodulatory cytokines such as IL-4, IL-10, or TGF-beta, In this wo rk we have attempted to extend this paradigm to man by analyzing the respon se of human PF T cells to in vitro challenge with the common dietary Ag bet a -lactoglobulin (beta lg) of cow's milk. PP T cells stimulated with beta l g showed enhanced proliferation compared with blood T cells from the same p atient. Increased expression of CD25 and the Th1-associated chemokine recep tor CCR5 was also seen on CD4(+) and CD8(+) PP T cells, but not blood T cel ls, stimulated with beta lg, By enzyme-linked immunospot assay and RT-PCR, the PP T cell recall response to beta lg and casein was dominated by IFN-ga mma, with negligible IL-4, IL-5, IL-10, or TGF-beta, To help explain the PP T cell response to beta lg, we examined IL-12 expression. Both IL-12p40 an d -p35 transcripts were abundantly expressed in PP, but not in adjacent nor mal ileal mucosa, Immunoreactive IL-12p40-containing cells were present bel ow the PP dome epithelium. Furthermore, in culture, FP, but not paired PBMC , spontaneously released IL-12p70, These results suggest that the human res ponse to oral Ags in the gut may be different from that in rodents.