title: Functional transforming growth factor-β receptor type II expression by CD4+ T cells in Peyer's patches is essential for oral tolerance induction.
abstract: Our previous studies have shown that Peyer's patches (PPs) play a key role in the induction of oral tolerance. Therefore, we hypothesized that PPs are an important site for Transforming Growth Factor (TGF)-β signaling and sought to prove that this tissue is of importance in oral tolerance induction. We found that expression of TGF-β type II receptor (TGFβRII) by CD4(+) T cells increases and persists in the PPs of normal C57BL/6 mice after either high- or low-dose feeding of OVA when compared to mesenteric lymph nodes (MLNs) and spleen. Approximately one-third of these TGFβRII(+) CD4(+) T cells express the transcription factor Foxp3. Interestingly, the number of TGFβRII(+) CD4(+) T cells in PPs decreased when OVA-fed mice were orally challenged with OVA plus native cholera toxin (CT). In contrast, numbers of TGFβRII(+) CD4(+) T cells were increased in the intestinal lamina propria (iLP) of these challenged mice. Further, these PP CD4(+) TGFβRII(+) T cells upregulated Foxp3 within 2 hours after OVA plus CT challenge. Mice fed PBS and challenged with OVA plus CT did not reveal any changes in TGFβRII expression by CD4(+) T cells. In order to test the functional property of TGFβRII in the induction of oral tolerance, CD4dnTGFβRII transgenic mice, in which TGFβRII signaling is abrogated from all CD4(+) T cells, were employed. Importantly, these mice could not develop oral tolerance to OVA. Our studies show a critical, dose-independent, role for TGFβRII expression and function by CD4(+) T cells in the gut-associated lymphoid tissues, further underlining the vital role of PPs in oral tolerance.
authors.affiliation: The Immunobiology Vaccine Center, The Department of Microbiology, The University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
authors.forename: Rebekah S
authors.initials: RS
authors.lastname: Gilbert
authors.forename: Ryoki
authors.initials: R
authors.lastname: Kobayashi
authors.forename: Shinichi
authors.initials: S
authors.lastname: Sekine
authors.forename: Kohtaro
authors.initials: K
authors.lastname: Fujihashi
mesh_terms: D000284:Administration, Oral; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D015870:Gene Expression; D007108:Immune Tolerance; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology; D010581:Peyer's Patches / Q000276:immunology*; D017346:Protein Serine-Threonine Kinases / Q000032:analysis* / Q000235:genetics; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000032:analysis* / Q000235:genetics; D015398:Signal Transduction / Q000276:immunology
chemical_list: D018125:Receptors, Transforming Growth Factor beta; D010047:Ovalbumin; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II
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