Homing of human autoreactive T cells into pancreatic tissue of NOD-scid mice

Halteren, Astrid G. S. van; Kardol, M. J.; Mulder, Arend; Roep, Bart O.

doi:10.1007/s00125-004-1613-2

Cited by 35 publications

(26 citation statements)

References 51 publications

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“…This observation coupled with the findings made in the current study, suggest that T cell clones mediating islet graft destruction are directly recruited from PBL. Further evidence indicating that clonotypes found in PBL exhibit a diabetogenic capacity is provided by Roep and colleagues (24) who showed that ␤ cell-specific CD4 ϩ T cell clones prepared from PBL of diabetic patients readily traffick to the islets after transfer into NOD.scid mice.…”

Section: Discussionmentioning

confidence: 98%

Identical β Cell-Specific CD8+ T Cell Clonotypes Typically Reside in Both Peripheral Blood Lymphocyte and Pancreatic Islets

Wong

Stevens

Long

et al. 2007

The Journal of Immunology

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A major issue regarding T cell responses in autoimmunity is how the repertoire compares between the periphery and target organ. In type 1 diabetes, the status of at-risk or diabetic individuals can be monitored by measuring β cell-specific T cells isolated from PBL, but whether these T cells accurately reflect the repertoire residing in the pancreatic islets is unclear. The TCR repertoire of disease-relevant, tetramer-sorted CD8+ T cells was examined at the single-cell level in PBL, pancreatic lymph nodes (PLN), and the islets of individual NOD mice. CDR3α and CDR3β sequences demonstrated that the same repertoire of T cells in PBL was detected in the islets and PLN, although the frequency of specific clonotypes varied. Albeit infrequent, clonotypes that were prevalent in the islets but not found in PBL were also detected. β cell Ag immunization expanded immunodominant PBL clonotypes present in the islets and PLN. These results show that insight into repertoire profiles of islet-infiltrating T cells can be obtained from PBL.

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Section: Discussionmentioning

confidence: 98%

Identical β Cell-Specific CD8+ T Cell Clonotypes Typically Reside in Both Peripheral Blood Lymphocyte and Pancreatic Islets

Wong

Stevens

Long

et al. 2007

The Journal of Immunology

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show abstract

“…Moreover, T-cell clones have been produced from peripheral blood mononuclear cells of newly diagnosed patients that are home to the pancreas of NOD-SCID mice after intravenous transfer, suggesting that autoreactive T-cells circulate at the periphery. 35 Evidence shows that transcriptome analysis will offer new opportunities to identify genes that can be used for early diagnosis of diabetes. Recently, through the combined approach of microarray profiling and genetic linkage analysis, it has been shown that gene expression patterns can be inherited under a variety of conditions across a range of species.…”

Section: Discussionmentioning

confidence: 99%

Specific gene expression signature associated with development of autoimmune type-I diabetes using whole-blood microarray analysis

et al. 2010

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Understanding the pathogenesis of type-I diabetes (T1D) is hindered in humans by the long autoimmune process occurring before clinical onset and by the difficulty to study the pancreas directly. Alternatively, exploring body fluids and particularly peripheral blood can provide some insights. Indeed, circulating cells can function as 'sentinels', with subtle changes in gene expression occurring in association with disease. Therefore, we investigated the gene expression profiles of circulating blood cells using Affymetrix microarrays. Whole-blood samples from 20 first-degree relatives of T1D children with autoimmune diabetes-related antibodies, 19 children immediately after the onset of clinical T1D and 20 age-and sex-matched healthy controls were collected in PAXgene tubes. A global gene expression analysis with MDS approach allowed the discrimination of pre-diabetic subjects, diabetic patients and healthy controls. Univariate statistical analysis highlighted 107 distinct genes differently expressed between these three groups. Two major gene expression profiles were characterized, including type-I IFN-regulated genes and genes associated with biosynthesis and oxidative phosphorylation. Our results showed the presence of early functional modifications associated with T1D, which could help to understand the disease and suggest possible avenues for therapeutic interventions.

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“…When islets with two or more infiltrating T cells cells of islet infiltrating T cells in a rodent model [10].…”

Section: Expression Of Cxcr3mentioning

confidence: 99%

Expression of chemokines, CXC chemokine ligand 10 (CXCL10) and CXCR3 in the inflamed islets of patients with recent-onset autoimmune type 1 diabetes

et al. 2010

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Homing of human autoreactive T cells into pancreatic tissue of NOD-scid mice

Cited by 35 publications

References 51 publications

Identical β Cell-Specific CD8+ T Cell Clonotypes Typically Reside in Both Peripheral Blood Lymphocyte and Pancreatic Islets

Identical β Cell-Specific CD8+ T Cell Clonotypes Typically Reside in Both Peripheral Blood Lymphocyte and Pancreatic Islets

Specific gene expression signature associated with development of autoimmune type-I diabetes using whole-blood microarray analysis

Expression of chemokines, CXC chemokine ligand 10 (CXCL10) and CXCR3 in the inflamed islets of patients with recent-onset autoimmune type 1 diabetes

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