In situ islet T cell receptor variable region gene usage in the nonobese diabetic mouse

Toyoda, Hiroo; Redford, Andreea; Magalong, D.; Chan, Erwin; Hosszúfalusi, Nóra; Formby, Bent; Teruya, Masanori; Charles, M. Arthur

doi:10.1016/0165-2478(92)90056-t

Cited by 11 publications

(6 citation statements)

References 22 publications

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“…These autoreactive T cells could be detected before acute inflammation occurred. This hypothesis is supported by our recent observation using mouse type I diabetes model, NOD mouse, demonstrating that only limited TCR gene usage can be observed before the onset of disease [18], Therefore, in our study, T cells expressing a particular v p chain of TCR result from the compartmentalized selection in the lung microenvironment in which the SHP inflammatory process takes place. In ad dition, when BAL lymphocytes obtained from patients with bird fancier's lung were cultured in the presence of pigeon serum, the poylclonal TCR expression was observed (data not shown).…”

Section: Discussionsupporting

confidence: 74%

A Compartmentalized Bias for T-Cell Receptor Vβ Usage in Summer-Type Hypersensitivity Pneumonitis

Murayama

Yoshizawa²,

Sato³

et al. 1995

Int Arch Allergy Immunol

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Several monoclonal antibodies specific to the human T-cell receptor (TCR) variable (V) region were used to examine whether T-cell oligoclonality plays a key role in the development of the T-cell-mediated lung disease, summer-type hypersensitivity pneumonitis (SHP). The usage of TCR V-regions was examined using bronchoalveolar lavage (BAL) and matched peripheral blood lymphocytes (PBL) in patients with SHP. In 18 SHP patients, the majority of lymphocytes in both BAL and PBL was CD3⁺ cells (94.2 vs. 63.9%, respectively), which was similar to that in normals (n = 7). Of CD3⁺ lymphocytes in a SHP patient, the percentage of CD4⁺ cells in BAL was reduced compared to those in paired PBL, whereas the percentage of CD8⁺ cells was significantly elevated. In contrast, the percentage of CD4⁺ cells was much higher than that of CD8⁺ cells in both BAL and PBL of normal subjects. While a majority of CD3⁺ T cells expressed TCR α/β⁺ in BAL and PBL from both SHP patients and normal controls, a marked increase of the expression of TCR γ/δ⁺ was observed in PBL in 4 out of 18 SHP patients. A markedly increased prevalence (> 3 SD) of specific TCR α/β⁺ V-region families in BAL was detected in 5 of 18 patients with SHP as compared to normal controls, whereas no specific increase was found in PBL. Increased Vβ8 was detected in 3 cases; Vβ6 was observed in 1 patient, and Vβ5 in another patient. These results demonstrate a compartmentalization of T cells with limited TCR V-region repertoires in subgroups of patients with SHP suggesting an accumulation of T-cell clones using a limited number of TCR V-region genes in the lung.

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Section: Discussionsupporting

confidence: 74%

A Compartmentalized Bias for T-Cell Receptor Vβ Usage in Summer-Type Hypersensitivity Pneumonitis

Murayama

Yoshizawa²,

Sato³

et al. 1995

Int Arch Allergy Immunol

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“…The TCR Vβ repertoire of islet-infiltrating T cells has been investigated mostly by RT-PCR from bulk RNA isolated from the islets or via flow cytometric-sorted MHC multimer-binding T cells [20], [21], [32], [42], [46]–[56]. Studies using the former approach typically have not distinguished between naïve and eff/mem T cells.…”

Section: Discussionmentioning

confidence: 99%

Autoreactive Effector/Memory CD4+ and CD8+ T Cells Infiltrating Grafted and Endogenous Islets in Diabetic NOD Mice Exhibit Similar T Cell Receptor Usage

et al. 2012

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Islet transplantation provides a “cure” for type 1 diabetes but is limited in part by recurrent autoimmunity mediated by β cell-specific CD4+ and CD8+ T cells. Insight into the T cell receptor (TCR) repertoire of effector T cells driving recurrent autoimmunity would aid the development of immunotherapies to prevent islet graft rejection. Accordingly, we used a multi-parameter flow cytometry strategy to assess the TCR variable β (Vβ) chain repertoires of T cell subsets involved in autoimmune-mediated rejection of islet grafts in diabetic NOD mouse recipients. Naïve CD4+ and CD8+ T cells exhibited a diverse TCR repertoire, which was similar in all tissues examined in NOD recipients including the pancreas and islet grafts. On the other hand, the effector/memory CD8+ T cell repertoire in the islet graft was dominated by one to four TCR Vβ chains, and specific TCR Vβ chain usage varied from recipient to recipient. Similarly, islet graft- infiltrating effector/memory CD4+ T cells expressed a limited number of prevalent TCR Vβ chains, although generally TCR repertoire diversity was increased compared to effector/memory CD8+ T cells. Strikingly, the majority of NOD recipients showed an increase in TCR Vβ12-bearing effector/memory CD4+ T cells in the islet graft, most of which were proliferating, indicating clonal expansion. Importantly, TCR Vβ usage by effector/memory CD4+ and CD8+ T cells infiltrating the islet graft exhibited greater similarity to the repertoire found in the pancreas as opposed to the draining renal lymph node, pancreatic lymph node, or spleen. Together these results demonstrate that effector/memory CD4+ and CD8+ T cells mediating autoimmune rejection of islet grafts are characterized by restricted TCR Vβ chain usage, and are similar to T cells that drive destruction of the endogenous islets.

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“…Activation Arise in NOD Mice, and Is This 1992; Toyoda et al, 1992;Galley and Danska, 1995;Daniel and Wegmann, 1996;Komagata et al, 1996 1987;Christianson et al, 1993) and that islet ␤ cell destruction is mediated by both CD4 ϩ (Haskins and 1 month of age and even prior to insulitis. As previously demonstrated, islet-infiltrating CD4 ϩ T cells examined McDuffie, 1990;Christianson et al, 1993;Rohane et al, 1995) and CD8 ϩ (Wicker et al, 1995;Kay et al, 1996; at the time of insulitis express a heterogeneous array of TCR variable (V) ␤ gene products (Maeda et al, 1991;Wong et al, 1996) T cells.…”

Section: Does An Imbalance Between Thl and Th2 Cellmentioning

confidence: 99%

“…Is there evidence for molecular mimicry in T cell-are able to activate low-level effector T cell responses in NOD mice (Haskins et al, 1989) and that relatively mediated autoimmune disease? It is known that experimental acute and persistent infections with DNA or RNA few peptides can be eluted from I-A g7 molecules (Reich et al, 1994).…”

mentioning

confidence: 99%

The Nonobese Diabetic Mouse as a Model of Autoimmune Diabetes: Immune Dysregulation Gets the NOD

1997

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In situ islet T cell receptor variable region gene usage in the nonobese diabetic mouse

Cited by 11 publications

References 22 publications

A Compartmentalized Bias for T-Cell Receptor Vβ Usage in Summer-Type Hypersensitivity Pneumonitis

A Compartmentalized Bias for T-Cell Receptor Vβ Usage in Summer-Type Hypersensitivity Pneumonitis

Autoreactive Effector/Memory CD4+ and CD8+ T Cells Infiltrating Grafted and Endogenous Islets in Diabetic NOD Mice Exhibit Similar T Cell Receptor Usage

The Nonobese Diabetic Mouse as a Model of Autoimmune Diabetes: Immune Dysregulation Gets the NOD

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