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 produce immunomodulatory cytokines such as IL-4, IL-10, or TGF-beta. 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 beta-lactoglobulin (betalg) of cow's milk. PP T cells stimulated with betalg 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 betalg. By enzyme-linked immunospot assay and RT-PCR, the PP T cell recall response to betalg and casein was dominated by IFN-gamma, with negligible IL-4, IL-5, IL-10, or TGF-beta. To help explain the PP T cell response to betalg, 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.
Nagata
S
S
Department of Pediatric Gastroenterology, St. Bartholomews and the Royal London School of Medicine, St. Bartholomews Hospital, London, United Kingdom.
McKenzie
C
C
Pender
S L
SL
Bajaj-Elliott
M
M
Fairclough
P D
PD
Walker-Smith
J A
JA
Monteleone
G
G
MacDonald
T T
TT
D000293:Adolescent; D000328:Adult; D000941:Antigens / Q000008:administration & dosage* / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000032:analysis / Q000096:biosynthesis*; D004044:Dietary Proteins / Q000008:administration & dosage / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007082:Ileum / Q000737:chemistry / Q000276:immunology; D018664:Interleukin-12 / Q000032:analysis; D007413:Intestinal Mucosa / Q000737:chemistry / Q000276:immunology; D007782:Lactoglobulins / Q000008:administration & dosage / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D010581:Peyer's Patches / Q000737:chemistry / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D011446:Prospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism*
D000941:Antigens; D016207:Cytokines; D004044:Dietary Proteins; D007782:Lactoglobulins; D018664:Interleukin-12