Selective induction of Th2 cells in murine Peyer's patches by oral immunization

Abstract

We have used three different methods to determine the T helper (Th) cell response, including Th1 and Th2 types, in murine Peyer's patches (PP) following oral immunization with sheep red blood cells (SRBC). These include: (i) use of cytokine-specific (IFN-gamma and IL-5), single cell assays to estimate the frequencies of Th1 and Th2 cells respectively, (ii) cytokine-specific mRNA--cDNA dot blot and Northern gel hybridizations to detect levels of specific mRNA, and (iii) T cell cloning techniques to determine the frequency of Th1 and Th2 clones. Mice were immunized with SRBC by either the oral or i.p. route. The PP and splenic (SP) CD3+ and CD3+ CD4+ T cell subsets were isolated and cultured with antigen, feeder cells, and IL-2, and were assessed at various intervals (days 0, 1, 3, and 6) for numbers of T cells producing either IFN-gamma or IL-5 by use of an enzyme-linked immunospot (ELISPOT) procedure. Cultures of T cells from PP or SP of mice given SRBC by the oral route had a high frequency of IL-5 spot forming cells (SFC), with lower numbers of IFN-gamma SFC. However, cultures of CD3+ T cells and CD3+ CD4+ Th cells from spleens of i.p. immunized mice exhibited predominantly IFN-gamma SFC, with smaller but significant numbers of IL-5 SFC. This distinct pattern of cytokine production was supported by mRNA analysis where high IL-5 specific mRNA levels were noted in PP T cell cultures of orally primed mice, while IFN-gamma mRNA was predominant in the SP CD3+ T cell and CD3+ CD4+ Th cell cultures from i.p. immunized mice. When the frequencies of IFN-gamma or IL-5 SFC were assessed among cloned Th cells from orally- or systemically-immunized mice, 74% of Th cell clones from PP of mice orally immunized with SRBC were IL-5 producers (Th2 type), while 67% of Th cell clones from SP of mice immunized by the i.p. route were IFN-gamma producers (Th1 type). Our studies show that higher frequencies of IFN-gamma producing Th1-type cells occur in SP of mice given antigen by the systemic route, while oral immunization results in predominantly IL-5 producing, Th2-type cells in PP.

M cell-targeted DNA vaccination

“…In addition, the prolonged IgA responses resembled the observed time course described for oral immunization with microencapsulated DNA (18,33,34). As formulated, the mucosal delivery of the protein 1-PL-DNA favored Th2-type cytokine responses consistent with previous reports that vaccination of mucosal surfaces favors Th2-type development (12,35,36). The reason for this preferential Th2-type bias is unclear, because a recent report showed that i.n.…”

Antigen Presentation by Peyer's Patch Cells Can Induce both Th1- and Th2-type Responses Depending on Antigen Dosage, but a Different Cytokine Response Pattern from That of Spleen Cells

“…PP is an intestinal lymphoid organ and is characterized as an inductive site of mucosal-type immune responses such as Th2 cytokines and transforming growth factor (TGF-b) secretion. 14,15) It has been reported that DC in PP preferentially induced Th2 cytokines, while SPL DC induced Th1 cytokines. 9,10) Our present study shows that antigen presentation by whole PP cells could induce both Th1-and Th2-type cytokine patterns.…”

Early Intestinal Th1 Inflammation and Mucosal T Cell Recruitment During Acute Graft-Versus-Host Reaction

“…IL-5 is often considered a Th2-type cytokine (48,49). However, its exact regulation in relation to IL-4 production in the intestine is not clearly understood, and to this point it has not been studied in intestinal GVHR.…”