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Department of Pediatric Gastroenterology, St. Bartholomews and the Royal London School of Medicine, St. Bartholomews Hospital, London, United Kingdom;
Digestive Diseases Research Center, St. Bartholomews and the Royal London School of Medicine, The Royal London Hospital, London, United Kingdom; and
Department of Pediatric Gastroenterology, Royal Free Hospital, London, United Kingdom
Animal studies have demonstrated that feeding Ags induces
regulatory (Th2, Th3) cells in Peyer’s patches (PP), which migrate to
the periphery and produce immunomodulatory cytokines such as IL-4,
IL-10, or TGF-ß. In this work we have attempted to extend this
paradigm to man by analyzing the response of human PP T cells to in
vitro challenge with the common dietary Ag ß-lactoglobulin (ßlg) of
cow’s milk. PP T cells stimulated with ßlg showed enhanced
proliferation compared with blood T cells from the same patient.
Increased expression of CD25 and the Th1-associated chemokine receptor
CCR5 was also seen on CD4+ and CD8+ PP T cells,
but not blood T cells, stimulated with ßlg. By enzyme-linked
immunospot assay and RT-PCR, the PP T cell recall response to ßlg and
casein was dominated by IFN-
, with negligible IL-4, IL-5, IL-10, or
TGF-ß. To help explain the PP T cell response to ßlg, we examined
IL-12 expression. Both IL-12p40 and -p35 transcripts were
abundantly expressed in PP, but not in adjacent normal ileal mucosa.
Immunoreactive IL-12p40-containing cells were present below the PP dome
epithelium. Furthermore, in culture, PP, but not paired PBMC,
spontaneously released IL-12p70. These results suggest that the human
response to oral Ags in the gut may be different from that in
rodents.
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