Functional transforming growth factor-? 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)-? signaling and sought to prove that this tissue is of importance in oral tolerance induction. We found that expression of TGF-? type II receptor (TGF?RII) 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 TGF?RII(+) CD4(+) T cells express the transcription factor Foxp3. Interestingly, the number of TGF?RII(+) CD4(+) T cells in PPs decreased when OVA-fed mice were orally challenged with OVA plus native cholera toxin (CT). In contrast, numbers of TGF?RII(+) CD4(+) T cells were increased in the intestinal lamina propria (iLP) of these challenged mice. Further, these PP CD4(+) TGF?RII(+) 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 TGF?RII expression by CD4(+) T cells. In order to test the functional property of TGF?RII in the induction of oral tolerance, CD4dnTGF?RII transgenic mice, in which TGF?RII 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 TGF?RII expression and function by CD4(+) T cells in the gut-associated lymphoid tissues, further underlining the vital role of PPs in oral tolerance.

SUBMITTER: Gilbert RS 

PROVIDER: S-EPMC3210179 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature