The effect of weaning on the clonality of αβ T-cell receptor T cells in the intestine of GF and SPF mice

Probert, Chris; Williams, Amanda; Štěpánková, Renata; Tlaskalová‐Hogenová, Helena; Phillips, Anne; Bland, Paul W.

doi:10.1016/j.dci.2006.08.008

Cited by 15 publications

(19 citation statements)

References 33 publications

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“…However, this phenomenon was more dramatic in DM mice (Figure 2A,B). In blood samples obtained at 7 months, the percentage of CD8m among CD8 T cells was 42.7% (Ϯ 19.1%), 29.2% (Ϯ 10.5%), 25.1% (Ϯ 9.7%), and 18.4% (Ϯ 4.7%) for the DM, Tg, Htz, and WT mice, respectively ( Figure 2B). DM mice had higher levels of CD8m compared with mice with the other genotypes, but this difference was significant only in comparison to nontransgenic animals (vs Htz: P ϭ .023; vs WT: P ϭ .003).…”

Section: Results 12p13 Deletion In Human T-pllmentioning

confidence: 99%

“…25,27 In this technique, T-cell diversity is evaluated according to the CDR3 size pattern generated by the Tcrb V(D)J recombination, analyzing rearrangements using each of the 20 V␤ segments separately. Patterns were examined for each V␤, and the presence of a clone was determined according to the presence of a highest peak representing more than 70% of all the peaks of the Gaussian curve.…”

Section: Nature Of the Cellular Expansions In Cdkn1b ؉/؊ /Mtcp1 Tg Micementioning

confidence: 99%

“…CDR3 spectratyping used to define the clonality of the T-cell population was performed as described by Probert et al, 25 but omitting the amplification step by nested PCR. Briefly, PCRs were performed using one of 2 different labeled C␤ primers (-HEX and -FAM) and one of the 20 unlabeled primers corresponding to the 20 V␤ segments, allowing amplification of all the murine Tcrb rearranged transcripts.…”

Section: Cdr3 Spectratypingmentioning

confidence: 99%

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Haploinsufficiency of CDKN1B contributes to leukemogenesis in T-cell prolymphocytic leukemia

Toriellec

Despouy

Pierron

et al. 2008

Blood

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T-cell prolymphocytic leukemia (T-PLL) isconsistently associated with inactivation of the ATM gene and chromosomal rearrangements leading to an overexpression of MTCP1/TCL1 oncoproteins. These alterations are present at the earliest stage of malignant transformation, suggesting that additional events are required for overt malignancy. In this study, we pursued the investigation of the 12p13 deletion, previously shown to occur in approximately half of T-PLLs. We refined the minimal region of deletion by single nucleotide and microsatellite polymorphism allelotyping. We defined a 216-kb region containing the CDKN1B gene that encodes the cyclin-dependent kinase inhibitory protein p27 KIP1 . Sequencing this gene in 47 T-PLL patient samples revealed a nonsense mutation in one case without 12p13 deletion. The absence of biallelic inactivation of CDKN1B for most patients suggested a haploinsufficiency mechanism for tumor suppression, which was investigated in an animal model of the disease. In a Cdkn1b ϩ/Ϫ background, MTCP1 transgenics had consistent and multiple emergences of preleukemic clones not observed in control cohorts. The second Cdkn1b allele was maintained and expressed in these preleukemic clones. Altogether, these data strongly implicate CDKN1B haploinsufficiency in the pathogenesis of T-PLL. IntroductionT-cell prolymphocytic leukemia (T-PLL) is a rare hematologic disease of elderly people characterized by a mature T-cell phenotype, a large tumoral mass, and an aggressive clinical course. Two genetic alterations are known to play a major role in this disease. First, ATM is somatically deleted or mutated in almost 95% of T-PLL patients (for review, see Stankovic et al 1 ), and germinal mutations of ATM responsible for the ataxia telangiectasia (AT) predispose to T-PLL (for review, see Taylor et al 2 ). Second, chromosomal translocations and inversions involving TCR genes and MTCP1/TCL1 gene family members are consistently and specifically associated with T-PLL, leading to overexpression of these oncogenes. 3,4 The oncogenic role of the MTCP1/TCL1 genes was demonstrated using transgenic mouse models. 5,6 Recently, we showed that MTCP1/TCL1 oncogene expression modified T-cell homeostasis, 7 which may be related to the impairment of activationinduced cell death (AICD) by these oncoproteins. 8 ATM inactivation and MTCP1/TCL1 overexpression are present at the earliest stage of the malignant transformation in clonal T-cell populations frequently found in AT patients. However, the indolent course of these populations suggests that these events are insufficient to induce a leukemic phenotype. 9 In the search for additional events crucial for full-blown transformation, we undertook a comparative genomic hybridization analysis in a series of T-PLL cases that revealed numerous recurrent copy number alterations. 10 One of these alterations was the deletion of the 12p13 region, which was further characterized by allelotyping. This deletion was shown to occur in almost half of T-PLL cases and the minimal region of delet...

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Section: Results 12p13 Deletion In Human T-pllmentioning

confidence: 99%

Section: Nature Of the Cellular Expansions In Cdkn1b ؉/؊ /Mtcp1 Tg Micementioning

confidence: 99%

Section: Cdr3 Spectratypingmentioning

confidence: 99%

See 1 more Smart Citation

Haploinsufficiency of CDKN1B contributes to leukemogenesis in T-cell prolymphocytic leukemia

Toriellec

Despouy

Pierron

et al. 2008

Blood

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“…13,14 In addition, commensal bacteria promote angiogenesis and the development of the intestinal epithelium. 13 Meanwhile, studies using germ-free animals have illustrated the importance of commensal bacteria in the development of the gut-associated lymphoid tissues (GALT; reviewed previously [15][16][17] ). The beneficial effects of the microflora have resulted in the selection of specific species with putative health-promoting capabilities for the treatment of conditions where the gut bacteria compositions were disrupted.…”

Section: Outer Mucosal Barrier Components Commensal Microbiotamentioning

confidence: 99%

Importance of disrupted intestinal barrier in inflammatory bowel diseases

Salim

Söderholm

2011

Inflammatory Bowel Diseases

505

342

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The current paradigm of inflammatory bowel diseases (IBD), both Crohn's disease (CD) and ulcerative colitis (UC), involves the interaction between environmental factors in the intestinal lumen and inappropriate host immune responses in genetically predisposed individuals. The intestinal mucosal barrier has evolved to maintain a delicate balance between absorbing essential nutrients while preventing the entry and responding to harmful contents. In IBD, disruptions of essential elements of the intestinal barrier lead to permeability defects. These barrier defects exacerbate the underlying immune system, subsequently resulting in tissue damage. The epithelial phenotype in active IBD is very similar in CD and UC. It is characterized by increased secretion of chloride and water, leading to diarrhea, increased permeability via both the transcellular and paracellular routes, and increased apoptosis of epithelial cells. The main cytokine that seems to drive these changes is tumor necrosis factor alpha in CD, whereas interleukin (IL)-13 may be more important in UC. Therapeutic restoration of the mucosal barrier would provide protection and prevent antigenic overload due to intestinal "leakiness." Here we give an overview of the key players of the intestinal mucosal barrier and review the current literature from studies in humans and human systems on mechanisms underlying mucosal barrier dysfunction in IBD.

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“…24,46 Interestingly, the Tcell receptor repertoire is also influenced by colonization with microorganisms. 47 Recently we have studied the effect of the microbiota on the development of lymphatic subpopulations in BALB/c mice bred in Gut microbiota and mucosal barrier diseases H Tlaskalová -Hogenová et al 112 germ-free isolators or under conventional conditions and fed with sterile diets differing in contamination with microbial components. This study of lymphocyte subpopulations showed the mesenteric lymph nodes and Peyer's patches of germ-free mice fed by diets with lower lipopolysaccharide content contained fewer CD4…”

Section: The Role Of the Microbiota In Postnatal Development Of Innatmentioning

confidence: 99%

The role of gut microbiota (commensal bacteria) and the mucosal barrier in the pathogenesis of inflammatory and autoimmune diseases and cancer: contribution of germ-free and gnotobiotic animal models of human diseases

et al. 2011

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The effect of weaning on the clonality of αβ T-cell receptor T cells in the intestine of GF and SPF mice

Cited by 15 publications

References 33 publications

Haploinsufficiency of CDKN1B contributes to leukemogenesis in T-cell prolymphocytic leukemia

Haploinsufficiency of CDKN1B contributes to leukemogenesis in T-cell prolymphocytic leukemia

Importance of disrupted intestinal barrier in inflammatory bowel diseases

The role of gut microbiota (commensal bacteria) and the mucosal barrier in the pathogenesis of inflammatory and autoimmune diseases and cancer: contribution of germ-free and gnotobiotic animal models of human diseases

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