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Microbial induction of B and T cell areas in rabbit appendix.

ABSTRACT: Gut-associated lymphoid tissue (GALT) development requires interaction with the intestinal microbiota. Because murine secondary lymphoid tissue development is driven by positive feedback interactions between B cells and stromal cells, we used in situ hybridization to determine whether intestinal commensals influence such interactions during rabbit appendix development. The features of positive feedback interactions we examined (CXCL13 mRNA expression, B cell accumulation and FDC differentiation) increased during early follicle development, but stalled in the absence of intestinal commensals. These features were reinitiated by commensals that stimulated follicle development and intrafollicular B cell proliferation. Our results suggest that rabbit appendix follicles develop in two phases: an initial phase of B cell recruitment to nascent follicles, possibly through positive feedback interactions, and a subsequent phase of intrafollicular B cell proliferation stimulated by intestinal commensals. In addition, we found that intestinal commensals stimulate appendix CCL21 mRNA expression and T cell area formation.

SUBMITTER: Hanson NB

PROVIDER: S-EPMC2408667 | biostudies-literature | 2008

REPOSITORIES: biostudies-literature

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Microbial induction of B and T cell areas in rabbit appendix.

Hanson Nicholas B NB Lanning Dennis K DK

Developmental and comparative immunology 20080225 8

Gut-associated lymphoid tissue (GALT) development requires interaction with the intestinal microbiota. Because murine secondary lymphoid tissue development is driven by positive feedback interactions between B cells and stromal cells, we used in situ hybridization to determine whether intestinal commensals influence such interactions during rabbit appendix development. The features of positive feedback interactions we examined (CXCL13 mRNA expression, B cell accumulation and FDC differentiation) ...[more]

PMID: 18329710

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Project description:BackgroundGoblet cell carcinoid (GCC) of the appendix is a rare neoplasm that share histological features of both adenocarcinoma and carcinoid tumor. While its malignant potential remains unclear, GCC's are more aggressive than conventional carcinoid. The clinical presentations of this neoplasm are also varied. This review summarizes the published literature on GCC of the appendix. The focus is on its diagnosis, histopathological aspects, clinical manifestations, and management.MethodsPublished studies in the English language between 1966 to 2004 were identified through Medline keyword search utilizing terms "goblet cell carcinoid," "adenocarcinoid", "mucinous carcinoid" and "crypt cell carcinoma" of the appendix.ResultsBased on the review of 57 published papers encompassing nearly 600 diagnosed patients, the mean age of presentation for GCC of the appendix was 58.89 years with equal representation in both males and females. Accurate diagnosis of this neoplasm requires astute observations within an acutely inflamed appendix as this neoplasm has a prominent pattern of submucosal growth and usually lacks the formation of a well-defined tumor mass. The mesoappendix was involved in 21.64% followed by perineural involvement in 2.06%. The most common clinical presentations in order of frequency were acute appendicitis in 22.5%; asymptomatic in 5.4%; non-localized abdominal pain in 5.15% and an appendicular mass in 3.09%. The most common surgical treatment of choice was appendectomy with right hemicolectomy in 34.70% followed by simple appendectomy in 24.57%. Concomitant distant metastasis at diagnosis was present in 11.16% of patients with the ovaries being the most common site in 3.60% followed by disseminated abdominal carcinomatosis in 1.03%. Local lymph node involvement was seen in 8.76% of patients at the time of diagnosis. The reported 5-year survival ranges from 60 % to 84%. GCC's of the appendix remains a neoplasm of unpredictable biological behavior and thus warrants lifelong surveillance for recurrence of the disease upon diagnosis and successful surgical extirpation.ConclusionGCC of the appendix is a rare neoplasm. Due to its wide range of presentation, this tumor should be considered as a possible diagnosis in many varied situations leading to abdominal surgery. Histopathological features such as increased number of Paneth cells, increased amount of mucin secretion and presence of pancreatic polypeptide may predict a more aggressive behavior. The advocated plan of management recommended for patients with tumors that involve the adjacent caecum or with high-grade tumors with histological features such as an increased mitotic rate involve initial appendectomy with completion right hemicolectomy due to the high possibility of local recurrence with intraperitoneal seeding prior to lymph node involvement and a 20% risk of metastatic behavior. In female patients with GCC of the appendix regardless of age, bilateral salpingo-oophorectomy is advocated. In cases with obvious spread of the disease chemotherapy, mostly with 5-FU and leucovorin is advised. Cytoreductive surgery with adjuvant intraperitoneal chemotherapy can offer improved survival in cases with advanced peritoneal dissemination.

Project description:IntroductionAppendicitis is one of the most common causes of acute abdominal surgery in children. The clinical course of appendicitis ranges from simple to complex appendicitis. The mechanisms underlying the heterogeneity of appendicitis in children remain largely unclear. Dysregulated T cell responses play an important role in several inflammatory diseases of the intestine, but the extend of T cell dysregulation in appendicitis in children is less well known.MethodsTo characterize appendiceal T cells in simple and complex appendicitis we performed in-depth immunophenotyping of appendiceal-derived T cells by flow cytometry and correlated this to appendiceal-derived microbiota analyses of the same patient.ResultsAppendix samples of twenty children with appendicitis (n = 8 simple, n = 12 complex) were collected. T cells in complex appendicitis displayed an increased differentiated phenotype compared to simple appendicitis, including a loss of both CD27 and CD28 by CD4+ T cells and to a lesser extent by CD8+ T cells. Frequencies of phenotypic tissue-resident memory CD69+CD4+ T cells and CD69+CD8+ T cells were decreased in children with complex compared to simple appendicitis, indicating disruption of local tissue-resident immune responses. In line with the increased differentiated phenotype, cytokine production of in particular IL-17A by CD4+ T cells was increased in children with complex compared to simple appendicitis. Furthermore, frequencies of IL-17A+ CD4+ T cells correlated with a dysregulation of the appendiceal microbiota in children with complex appendicitis.ConclusionIn conclusion, disruption of local T cell responses, and enhanced pro-inflammatory Th17 responses correlating to changes in the appendiceal microbiota were observed in children with complex compared to simple appendicitis. Further studies are needed to decipher the role of a dysregulated network of microbiota and Th17 cells in the development of complex appendicitis in children.

Dataset Information

Microbial induction of B and T cell areas in rabbit appendix.

Publications

Microbial induction of B and T cell areas in rabbit appendix.

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