Interactions of commensal gut microbes with subsets of B- and T-cells in the murine host

Hq, Jiang; Thurnheer, M. Christine; Zuercher, AW; Boĭko, N I; Bos, Nicolaas A.; Cebra, J J

doi:10.1016/j.vaccine.2003.11.022

Cited by 55 publications

(44 citation statements)

References 17 publications

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“…The microbiota is the major stimulus for the immune system [43,44] and there is a constant influx of microbes across the mucosal surfaces, as evidenced by a constant secretion into the urine of peptidoglycan breakdown products, and the presence of bacterial cell wall remains in spleen macrophages. GF animals are exposed to self-Ag, to food-Ag and to some dead bacteria present in the sterilized food [45].…”

Section: Discussionmentioning

confidence: 99%

Impaired regulatory T cell function in germ‐free mice

et al. 2006

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Regulatory T cells (Treg) are crucial for the maintenance of tolerance to auto-antigens and harmless exogenous antigens. Here, we studied the role of the commensal microbiota for the development and function of Treg. CD4 + CD25 + T cells were obtained from peripheral lymph nodes (PLN) and mesenteric lymph nodes (MLN) of germ-free (GF) and conventional (conv) NMRI mice and tested for phenotype and functional suppressive capacity. CD4 + CD25 + T cells from GF mice showed a lower relative gene expression of fork head box p3 gene (Foxp3) and were not as potent suppressors in vitro as CD4 + CD25 + T cells from conv animals. Intracellular staining for Foxp3 and CTLA-4 revealed proportional and regional differences in putative Treg subsets between conv and GF mice. Fewer of the CD4 + CD25 + T cells in GF MLN expressed Foxp3 and CTLA-4, while the expression of these markers was similar amongst the CD4 + CD25 + T cells in PLN of conv and GF mice. The largest difference between conv and GF Treg was observed in the liver draining celiac lymph node, where GF mice had fewer putative Treg as compared to conv mice. We propose that the presence of a microbial flora favors the development of a fully functional Treg population. IntroductionRegulatory T cells down-regulate unwanted and exaggerated immune reactions to auto-antigens as well as innocuous environmental antigens. Different subsets of Treg have been defined. Natural CD4 + CD25 + Treg are positively selected for tissue-specific self-Ag in the thymus and exert their suppressive effect by cell-cell contact-dependent mechanisms [1]. Deficiency in the Treg population or neonatal thymectomy result in multiorgan autoimmune diseases [2][3][4][5][6][7][8]. Treg are characterized by a dense surface expression of CD25 (the a-chain of the IL-2-receptor), glucocorticoidinduced TNF receptor (GITR) and intracellular CTLA-4, however, these markers may be present on activated T cells. CD4 + CD25 + Tregs appear to be unique in transcribing the fork head box p3 gene (Foxp3) transcription factor [6,9], which enable their identification either with PCR are or newly developed mAb to the Foxp3 protein. Lack of a functional Foxp3 gene result in the severe autoimmune syndrome IPEX (immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome), characterized by organ-specific autoimmunity, colitis and high IgE levels [10,11]. Mice with spontaneous or induced mutations in the Foxp3 gene that impair Foxp3 expression fail to develop CD4 + CD25 + Treg and exhibit a syndrome similar to IPEX [5,6].Other subsets of Treg are induced in the periphery and are referred to as Th3 [12][13][14] and Tr1 cells [15][16][17][18][19] can also generate Treg. This implies that the state of the APC and the local cytokine milieu, e.g. in the normal gut where both IL-10 and TGF-b are abundant, can determine the outcome of an immune reaction, and that Treg are induced under these circumstances.The aim of this study was to investigate the phenotype and functionality of CD4 + CD25 + Treg from germ-free (GF) ...

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Section: Discussionmentioning

confidence: 99%

Impaired regulatory T cell function in germ‐free mice

et al. 2006

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“…In the experimental model employed here, the peritoneal B1-IgE + cells did not decrease during the evolution of the disease, indicating that their migration and homing are different from those observed for IgA + cells (33). Although only a fraction of IgE has been shown to be specific for the assayed schistosome antigens (31), the IgE response is apparently a part of the specific response to the infection, since its patterns follow the overall kinetics of the immune relationship between the host and the parasite.…”

Section: Discussionmentioning

confidence: 58%

IgE expression on the surface of B1 and B2 lymphocytes in experimental murine schistosomiasis

Oliveira

Aguiar

Borojević

et al. 2005

Braz J Med Biol Res

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In a previous study we monitored the distribution and phenotype expression of B1 cells during the evolution of experimental murine schistosomiasis mansoni and we proposed that the B1 cells were heterogeneous: a fraction which originated in the spleen and followed the migratory pathway to mesenteric ganglia, while the other was the resident peritoneal B1-cell pool. In the present study, we have addressed the question of whether these two B1-lymphocyte populations are involved in the production of the late Ig isotype IgE, which is present in high levels in schistosomal infection. Lymphocyte expression of surface markers and immunoglobulins were monitored by immunofluorescence flow cytometry. Both in the spleen and mesenteric ganglia, the B1 and B2 cells were induced to switch from IgM to IgE in the early Th2-dominated phase of the disease, with an increase of IgE in its later phases. Conversely, peritoneal B1-IgM + switched to the remaining IgE + present in high numbers in the peritoneal cavity throughout the disease. We correlated the efficient induction of the expression of late Ig isotypes by B1 cells with high levels of inflammatory cytokines due to the intense host response to the presence of worms and their eggs in the abdominal cavity. In conclusion, B1 cells have a different switch behavior from IgM to IgE indicating that these cell sub-populations depend on the microenvironment.

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“…The abundance of B cells in both ILF and PP compartments is highly dependent on enteric bacteria, as shown by their deficiency in germfree or antibiotic-treated mice, and their expansion in activation-induced cytidine deaminase Ϫ/Ϫ mice with impaired microbial control (8,15,17,18,26,68). However, whereas the formation of PP germinal centers was dependent on the presence of T lymphocytes, the formation of ILFs was not dependent on conventional or NK T cells (18).…”

Section: Discussionmentioning

confidence: 99%