Antigen sampling on the Peyer's patches in a murine small bowel transplantation model.

AIM: This study investigated changes in the mucosal barrier of transplanted intestines with particular emphasis on antigen sampling by Peyer's patches (PPs). METHODS: Heterotopic small bowel transplantation (SBTx) was performed as described previously. C57BL/6 mice were used as donors and BALB/c (allogeneic) or C57BL/6 mice (syngeneic) as recipients. Tacrolimus (FK506) or saline control was administered to the recipients for 2 weeks. Four groups included in this study were: syngeneic with or without immunosuppression (SYN and SYN + FK506, respectively) and allogeneic with or without immunosuppression (ALLO and ALLO + FK506, respectively). Animals were sacrificed weekly after SBTx to evaluate microfold (M) cells within PPs and for routine histology. By the third postoperative week, recipients were subjected to an intestine loop model to examine the uptake of microbeads by M cells as well as expression of Toll-like receptor 2 (TLR2) protein in the PPs with or without a TLR2 agonist challenge. We also measured occludin expression on follicle-associated epithelium (FAE) of PPs in the grafts. RESULTS: Transportation of microbeads through the PPs of the grafts increased in the ALLO + FK506 group compared with that in the SYN or SYN + FK506 group. This finding was accompanied by increased expression of TLR2 in the PPs and a gradually increased number of M cells following SBTx. However, occludin expression patterns on the FAE of the PPs in the grafts were similar among SYN, SYN + FK506, and ALLO + FK506 groups. Nevertheless, as transportation of microbeads and TLR2 expression in the PPs of the grafts was enhanced once exposed to Pam3Cys-SKKKK, similar results were not seen in the ALLO + FK506 group. CONCLUSIONS: Our study revealed that the mucosal barrier of intestinal grafts is altered under alloreactivity as evidenced by enhanced antigen sampling. Such a change may provide a pathway for translocation of microorganisms in the lumen.

The Peyer's patch microenvironment suppresses T cell responses to chemokines and other stimuli.

Immunosurveillance of mucosal sites presents immune cells with challenges not encountered in the periphery. T cells in the gut must distinguish enteric pathogens from innocuous non-self Ag derived from food or commensal bacteria. The mechanisms that regulate T cells in the gut remain incompletely understood. We assessed the effect of the Peyer's patch microenvironment on T cell responses to chemokines. Chemokines are believed to play an important role during T cell priming by facilitating T cell migration into and within lymphoid tissues as well as T cell encounter and interaction with APCs. We found a profound suppression of chemokine-stimulated T cell chemotaxis and actin polymerization in Peyer's patch relative to lymph node. Chemokine hyporesponsiveness is imposed upon T cells within hours of their entry into Peyer's patches and is reversed following their removal. Suppression was not restricted to chemokine stimulation, as T cell responses to Con A and PMA were also suppressed. The global nature of this defect is further underscored by an impairment in calcium mobilization. Evidence indicates that a soluble factor contributes to this hyporesponsiveness, and comparison of Peyer's patches and lymph nodes revealed striking differences in their chemokine and cytokine constitution, indicating a marked Th2 bias in the Peyer's patches. The role of the Th2 microenvironment in mediating suppression is suggested by the ability of Nippostrongylus brasiliensis to elicit hyporesponsiveness in lymph node T cells. The suppressive milieu encountered by T cells in Peyer's patches may be critical for discouraging undesired immune responses and promoting tolerance.

Size of jejunal Peyer's patches and migration of lymphocyte subsets in pigs after resection or transposition of the continuous ileal Peyer's patch.

In pigs there are two types of Peyer's patches in the small intestine: discrete patches in the jejunum (jejPP) and a continuous patch in the terminal ileum (ilPP). The ilPP was resectioned or transposed into the upper jejunum. After the operation the size of the remaining jejPP showed no compensatory growth in either group within 10 months. However, the number of CD8+ lymphocytes in the blood, spleen, mesenteric lymph nodes, tonsils, and Peyer's patches and the number of CD4+ cells in the spleen and tonsils was reduced in comparison to those of age-matched control pigs. Autologous blood lymphocytes were labelled with fluorescein isothiocyanate and retransfused. In control animals the mid-portion of the ilPP showed a lower entry of lymphocytes and the migration pattern of lymphocyte subsets was different in the animals with resectioned or transposed ilPP as compared to controls. Thus, the removal of the ilPP (about 60% of all small intestinal PP) did not result in the remaining patches adapting their size, but it did influence other lymphoid organs.

Heterotopic transplantation of syngeneic lymphoid tissues in mice. The ability of graft repopulation cells to enhance cell-mediated immunity as measured in the lymphocyte-induced angiogenesis assay.

Fragments of murine spleen and Peyer's patches were transplanted under the kidney capsule of syngeneic recipients. The ability of graft-repopulating cells to enhance cell-mediated immunity was tested in a lymphocyte-induced angiogenesis assay. The ability to evoke angiogenesis expressed by cells isolated from 10-day-old grafts of both tissues was significantly lower than that of cells isolated from organs in situ and was restored to control levels in both types of grafts 30 days after transplantation. Cells of Peyer's patch grafts showed weaker ability to induce angiogenesis than cells of spleen grafts regardless of the graft's age. Cells isolated from Peyer's patches in situ also showed weaker angiogenesis-inducing ability compared with normal spleen cells. Hence the results suggest that the repopulation of lymphoid tissue graft is specifically influenced by the graft's microenvironment.

Transplantation of the "presumptive" Peyer's patch of fetus or newborn mice under the kidney capsule of adult syngeneic recipient.

Small fragments of caecum from fetus, newborn or several-day-old mice were transplanted under the kidney capsule of adult syngeneic hosts. Transplants were derived from such a part of caecum at which in adult mice a Peyer's patch is always present (experimental group) or from such a part at which Peyer's patch is never located (control group). Donors were chosen from such early developmental stage at which Peyer's patches not yet been formed, hoping to observe Peyer's patch formation in transplants in view of possible influence of intestinal epithelium on a lymphocyte homing. After 10 to 150 days, transplants were asessed histologically. None Peyer's patche was formed. However, small accumulations of lymphoid cells were located in vicinity of epithelial cysts and blood vessels occasionally filled with lymphocytes were seen in the experimental but not in control group. The results showed that either number of epithelial cells or degree of their specialization were unsufficient for Peyer's patch formation. Other factors like the antigenic stimulation from the gut lumen might be thus necessary for Peyer's patch development.

Transplantation of Peyer's patches under the kidney capsule of syngeneic mice. The host origin of repopulating cells.

Peyer's patches were transplanted under the kidney capsule of syngeneic mice. After initial decrease in cellularity, the grafts were repopulated by lymphoid cells. Chromosomal marker analysis revealed that the host cells contribute mainly to the transplant repopulation.

Graft-versus-host reaction induced by Peyer's patches.

Parental Peyer's patches were implanted into the anterior hepatic lobe of F1 hybrid rats. Using conventional histological techniques, phenomena typical of a graft-versus-host reaction were observed, such as paravascular lymphoid infiltration in the liver, cellular depletion of the thymus-dependent areas of spleen, and diffuse reticuloendothelial cell proliferation in various lymphoid tissues. Based on these findings and other observations it is concluded that a thymus-dependent cell population is present in the Peyer's patches.

Cortisone sensitive T-cells in Peyers' patches.

Pretreatment of donor lymphoid cells with cortisone has been shown to depress the T-cell subpopulation responsible for cellular proliferation in the GVH reaction. A quantitative assay as well as the histological criteria of the GVH reaction have been used in this study to demonstrate the presence of cortisone-sensitive T-cells within the Peyer's patches as well as in the spleen and mesenteric lymph nodes in the rat.

Transplantation of Peyer's patches under the kidney capsule in syngeneic mice. I. Morphological studies.

The morphology of Peyer's patches transplanted under the kidney capsule in syngeneic mice was studied up to 30 days after transplantation. Changes undergoing in transplants were arbitrarily divided into three stages: the initial stage of necrosis, then from the third day on -- clearing of dead tissues, and finally, from the fifth day -- lymphoid regeneration. Starting from the ninth day on, the lymphoid structure of the transplants was quite distinct. Transplants appeared to be similar to Peyer's patches in situ. Reconstituted transplants contained a huge number of blood vessels located with lymphocytes. The epithelial cysts were found in all the transplants. They were formed by remnants of persisted intestinal epithelium covering Peyer's patches in situ. The possibility of epithelial influence on lymphoid regeneration of the transplants is discussed.