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Abstract: Peyer''s patches (PPs) are potential sites where specific mucosal immune responses and oral tolerance are induced. The unique features of these immune responses are thought to occur in micromilieu and are largely affected by antigen-presenting cells (APCs) such as dendritic cells. In this study, we investigated the cytokine profiles induced by the activation of CD4+ T cells of PPs. PP cells from TCR transgenic mice secreted greater amounts of IL-5 and IL-6 than spleen cells after antigenic stimulation. IL-5 was mainly produced by PP non-T cells, whereas IL-6 was secreted by PP CD4+ cells. PPs contained two major populations including naïve and memory/activated CD4+ cells; both populations secreted IL-6 upon activation. We also found that CD4+/CD62Lhi naïve cells from PPs secreted a greater amount of IL-6 after stimulation than those from the spleen. Furthermore, subtraction and qPCR analyses revealed that PP CD4+/CD62Lhi cells express a greater amount of transcripts of GA-binding protein β subunit 1 than those of the spleen. These results suggest that naïve T cells as well as non-T cells and activated/memory T cells from PPs are distinct from their splenic counterparts and thus cause unique immune responses the in intestine. [Copyright &y& Elsevier]

A T-cell receptor (TCR) antagonist is an analog of a peptide ligand for TCR that inhibits T-cell responses to the original peptide. We investigated the effects of a TCR antagonist on cytokine secretion of naive CD4+ T cells and their differentiation into type-1 and type-2 helper T cells (Th1 and Th2) induced by stimulation with varying doses of an antigenic peptide. In the presence of a TCR antagonist peptide, proliferation of naive CD4+ T cells and antigen dose-dependent secretion of interferon-γ, a typical Th1-type cytokine, by these cells was down-regulated. With respect to the secretion of interleukin-4 (IL-4), a typical Th2-type cytokine, the TCR antagonist raised the concentration of the antigenic peptide required to elicit maximal IL-4 production and, surprisingly, significantly increased the maximum level of IL-4 secretion. Similar effects induced by the TCR antagonist were observed on the Th1/Th2 differentiation of naive CD4+ T cells. These results clearly indicate that, for naive CD4+ T cells, a TCR antagonist has the potential to change the balance of Th1/Th2 cytokine secretion and even enhance Th2 responses. [Copyright &y& Elsevier]