Analysis of Function, Specificity and T Cell Receptor Expression of Cloned Mucosal T Cell Lines in Crohn's Disease

Prindiville, Thomas P; Cantrell, Mary C.; Matsumoto, Takayuki; Brown, William R.; Ansari, Aftab A.; Kotzin, Brian L.; Gershwin, M. Eric

doi:10.1006/jaut.1996.0023

Cited by 16 publications

(8 citation statements)

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“…Oligoclonal T‐cell expansions are found in pathogenic antigen‐driven immune responses, including autoimmune diseases and malignancies [35]. Many researchers have demonstrated oligoclonality with a limited TCR Vβ repertoire in CD4 + T‐cell populations from CD4 + T‐cell‐driven autoimmune diseases including autoimmune hepatitis [36], Crohn’s disease [37] and multiple sclerosis [38]. Concurrent CD8 + T‐cell oligoclonality has been shown for multiple sclerosis [39] and other autoimmune processes including aplastic anaemia [40] and juvenile dermatomyositis syndrome [41].…”

Section: Discussionmentioning

confidence: 99%

Vβ Usage and T Regulatory Cells in Children Following Partial or Total Thymectomy after Open Heart Surgery in Infancy

et al. 2009

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During open heart surgery in infants the thymus was usually removed, partly or completely. Our previous studies on 16 such children indicated reduced T‐cell output later in life with signs of extrathymic maturation of the T cells, but no reduction in T regulatory cells (CD4+CD25+). The diversity of the T‐cell repertoire in these children was examined to test if the extrathymic microenvironment could alter Vβ usage. The expression of Foxp3 and CD127 in CD4+CD25high T cells was measured in order to determine whether the T regulatory cells had the phenotype of natural T regulatory cells. There was a wide distribution of Vβ usage in both study and control groups. Significant variability was found in Vβ usage for CD4+ and CD8+ T cells when the distribution of the percentage of T cells expressing each Vβ family was analysed between individuals within each group (P < 0.001; Kruskal–Wallis). Significant difference was also found in average usage of Vβ2, Vβ5.1 and Vβ14 chains within CD4+ T cells and Vβ2, Vβ8 and Vβ21.3 chains within CD8+ cells between the groups (P < 0.05; Student’s t‐test). There was no difference between the two groups with regard to the proportion of CD4+CD25high T cells and no difference in the average expression of Foxp3 or CD127 within the CD4+CD25high population. Our data provide evidence that cardiothoracic surgery in infants and total or partial thymectomy alters Vβ usage, suggesting more limited selection in such children than in the control group. The frequency of natural T regulatory cells seems to be unimpaired.

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Section: Discussionmentioning

confidence: 99%

Vβ Usage and T Regulatory Cells in Children Following Partial or Total Thymectomy after Open Heart Surgery in Infancy

et al. 2009

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“…We have shown that human PBMCs containing TCR V␤ 5.1, 5.2, and 6.7 were significantly stimulated by rSEK in vitro. TCR V␤ 5.1 in particular has been observed to be overrepresented in several diseases of unknown etiology, in particular Crohn's disease, a severe small bowel inflammatory disorder (43). T cells from the V␤ 5 family have also been implicated in juvenile rheumatoid arthritis and periodontitis (32,37).…”

Section: Discussionmentioning

confidence: 99%

Biochemical and Biological Properties of Staphylococcal Enterotoxin K

et al. 2001

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Staphylococcus aureus is an important human pathogen which is implicated in a wide variety of diseases. Major determinants of the virulence of this organism include extracellular virulence factors. Staphylococcal enterotoxins (SEs) are important causative agents in staphylococcal toxic shock syndrome and food poisoning. Our study identified a novel enterotoxin, SEK, and examined its biochemical and biological properties. SEK had a molecular weight of 26,000 and an experimentally determined pI of between 7.0 and 7.5. SEK was secreted by clinical isolates of S. aureus. We demonstrated that SEK had many of the biological activities associated with the SEs, including superantigenicity, pyrogenicity, the ability to enhance the lethal effect of endotoxin, and lethality in a rabbit model when administered by subcutaneous miniosmotic pump. Recombinant SEK was shown to stimulate human CD4 ؉ and CD8 ؉ T cells in a V␤-specific manner; T-cells bearing V␤ 5.1, 5.2, and 6.7 were significantly stimulated to proliferate.

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“…TCR hVβ5 and hVβ6 domains, and especially hVβ5.1, have been shown to be overrepresented in patients with Crohn's disease, a severe inflammatory bowel syndrome 28 . These TCRs are also overrepresented in juvenile arthritis and periodontitis 29; 30 .…”

Section: Discussionmentioning

confidence: 99%

A Novel Loop Domain in Superantigens Extends their T Cell Receptor Recognition Site

Guenther

Varma

Moza

et al. 2007

Journal of Molecular Biology

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SummarySuperantigens (SAGs) interact with host immune receptors to induce a massive release of inflammatory cytokines that can lead to toxic shock syndrome and death. Bacterial SAGs can be classified into five distinct evolutionary groups. Group V SAGs are characterized by the α3-β8 loop, a unique ∼15 amino acid extension that is required for optimal T cell activation. Here, we report the X-ray crystal structures of the Group V SAG staphylococcal enterotoxin K (SEK) alone and in complex with the TCR hVβ5.1 domain. SEK adopts a unique TCR binding orientation relative to other SAG-TCR complexes which results in the α3-β8 loop contacting the apical loop of framework region 4 (FR4), thereby extending the known TCR recognition site of SAGs. These interactions are absolutely required for TCR binding and T cell activation by SEK and dictate the TCR Vβ domain specificity of SEK and other Group V SAGs.

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Analysis of Function, Specificity and T Cell Receptor Expression of Cloned Mucosal T Cell Lines in Crohn's Disease

Cited by 16 publications

References 0 publications

Vβ Usage and T Regulatory Cells in Children Following Partial or Total Thymectomy after Open Heart Surgery in Infancy

Vβ Usage and T Regulatory Cells in Children Following Partial or Total Thymectomy after Open Heart Surgery in Infancy

Biochemical and Biological Properties of Staphylococcal Enterotoxin K

A Novel Loop Domain in Superantigens Extends their T Cell Receptor Recognition Site

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