T-lymphocyte clone specific for pancreatic islet antigen

Haskins, Kathryn; Portas, M.; Bradley, Brenda J.; Wegmann, Dale; Lafferty, Kevin J.

doi:10.2337/diabetes.37.10.1444

Cited by 112 publications

(94 citation statements)

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“…The diabetogenic T cell clone BDC2.5 was derived from the spleen and lymph nodes of newly diabetic female mice as described previously (23). Cultures were restimulated every 2 wk by combining 1 ϫ 10 6 T cells, 2.5 ϫ 10 7 APCs (irradiated NOD spleen cells), 10 g ␤ cell membrane Ag (25), and human recombinant IL-2 (1000 U) in 20 ml of culture medium (IMDM) supplemented with 10% FBS.…”

Section: Propagation Of Bdc25mentioning

confidence: 99%

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Nondepleting Anti-CD4 Has an Immediate Action on Diabetogenic Effector Cells, Halting Their Destruction of Pancreatic β Cells

Phillips

Harach

Parish

et al. 2000

The Journal of Immunology

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The induction of tolerance in a primed immune system is a major aim for therapy in autoimmunity and transplant rejection. In this paper, we investigate the action of the nondepleting anti-CD4 Ab, YTS 177. Although this Ab is nondepleting, we have demonstrated a direct action in vivo on activated effector cells. We show that the Ab inhibits transfer of insulin-dependent diabetes mellitus by the CD4+ Th1 clone BDC2.5 to nonobese diabetic mice. Furthermore, we show that this Ab acts directly on diabetogenic effector cells because it prevented BDC2.5-induced insulin-dependent diabetes mellitus in nonobese diabetic-scid recipients in the absence of other T cells. The Ab halts the diabetic process even when it is administered after the BDC2.5 cells have infiltrated the pancreas and destruction of islets is already underway. This is accompanied by an immediate decrease in proinflammatory cytokine production with cessation of β cell destruction and disappearance of infiltrating cells from the pancreas, leaving any remaining β cells intact. These data suggest that Abs such as this may be effective not only because they induce regulatory T cells but also because they are able to directly prevent effector cell function.

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Section: Propagation Of Bdc25mentioning

confidence: 99%

“…To clarify this, we have conducted a detailed examination of the effect of nondepleting anti-CD4 Abs on the transfer of diabetes by the CD4 ϩ T cell clone BDC2.5 (23). This Th1 clone rapidly transfers diabetes to young NOD or NOD-scid mice, thus providing a model system to examine the role of anti-CD4.…”

mentioning

confidence: 99%

Nondepleting Anti-CD4 Has an Immediate Action on Diabetogenic Effector Cells, Halting Their Destruction of Pancreatic β Cells

Phillips

Harach

Parish

et al. 2000

The Journal of Immunology

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“…Even though the primary target antigen may not be known, in NOD mice pathogenic T cells have been shown to respond to various "antigens" including islets [23], beta-cell granules [24], GAD [25] and insulin [26], with a high frequency of insulin reactive T cells at the site of insulitis [27]. Furthermore, treatment of prediabetic NOD mice with insulin (oral, subcutaneous, intranasal) [28][29][30] or GAD (intravenous, intrathymic, intranasal) [31][32][33], delays, or even prevents the onset of IDDM.…”

mentioning

confidence: 99%

Altered immune response to insulin in newly diagnosed compared to insulin-treated diabetic patients and healthy control subjects

et al. 1997

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Insulin-dependent diabetes mellitus (IDDM) is the result of a genetically associated autoimmune mediated process in which the insulin-producing pancreatic beta-cells are thought to be destroyed by autoreactive T cells [1,2]. The disease process is accompanied by autoreactive T cells and autoantibodies to various islet antigens. Many IDDM patients develop humoral immune responses to insulin [3,4], islet cells [5], tyrosine phosphatase homologue islet cell antibody ((ICA)512/islet cell antigen (IA)-2, 37 K) [6-9] and glutamic acid decarboxylase (GAD)65 [10][11][12]. Even though autoantibodies may not be directly involved in the destructive process, 60 % of new-onset diabetic patients are positive for insulin autoantibodies (IAA) compared to only 0.5 % of healthy control subjects [2]. The involvement of T cells in the pathogenesis has been implicated by insulitis [13], the recurrence of insulitis and diabetes after pancreas transplantation [14] and the transfer of diabetes with non-T-cell-depleted bone marrow transplants

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“…Primary ␤ cells do not express class II MHC molecules. The mode of presentation of ␤-cell Ags is primarily via Ag-transfer mechanisms wherein the ␤-cell Ags are taken up by APCs, which process and present them to T cells (11)(12)(13). Moreover, the numbers of ␤ cells in pancreas is limited (ϳ10 5 ␤ cells per mouse), so using them for Ag transfer studies is difficult.…”

mentioning

confidence: 99%

First Signature of Islet β-Cell-Derived Naturally Processed Peptides Selected by Diabetogenic Class II MHC Molecules

Suri¹,

Walters

Rohrs

et al. 2008

The Journal of Immunology

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The diversity of Ags targeted by T cells in autoimmune diabetes is unknown. In this study, we identify and characterize a limited number of naturally processed peptides from pancreatic islet β-cells selected by diabetogenic I-Ag7 molecules of NOD mice. We used insulinomas transfected with the CIITA transactivator, which resulted in their expression of class II histocompatibility molecules and activation of diabetogenic CD4 T cells. Peptides bound to I-Ag7 were isolated and examined by mass spectrometry: some peptides derived from proteins present in secretory granules of endocrine cells, and a number were shared with cells of neuronal lineage. All proteins to which peptides were identified were expressed in β cells from normal islets. Peptides bound to I-Ag7 molecules contained the favorable binding motif characterized by acidic amino acids at the P9 position. The draining pancreatic lymph nodes of prediabetic NOD mice contained CD4 T cells that recognized three different natural peptides. Furthermore, four different peptides elicited CD4 T cells, substantiating the presence of such self-reactive T cells. The overall strategy of identifying natural peptides from islet β-cells opens up new avenues to evaluate the repertoire of self-reactive T cells and its role in onset of diabetes.

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T-lymphocyte clone specific for pancreatic islet antigen

Cited by 112 publications

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Nondepleting Anti-CD4 Has an Immediate Action on Diabetogenic Effector Cells, Halting Their Destruction of Pancreatic β Cells

Nondepleting Anti-CD4 Has an Immediate Action on Diabetogenic Effector Cells, Halting Their Destruction of Pancreatic β Cells

Altered immune response to insulin in newly diagnosed compared to insulin-treated diabetic patients and healthy control subjects

First Signature of Islet β-Cell-Derived Naturally Processed Peptides Selected by Diabetogenic Class II MHC Molecules

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