The T Cell Marker RT6 in a Rat Model of Autoimmune Diabetes

Greiner, Dale L.; Malkani, Samir; Kanaitsuka, Toshihiro; Bortell, Rita; Doukas, John; Rigby, Mark R.; Whalen, Barbara J.; Stevens, Linda A.; Moss, Joel; Mordes, John P.; Rossini, Aldo A.

doi:10.1007/978-1-4419-8632-0_26

Cited by 16 publications

(13 citation statements)

References 33 publications

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“…NADmediated apoptosis could thereby play a role in restricting the proliferation of bystander lymphocytes. This provides a plausible scheme for NAD to participate in the control of autoimmunity as already suggested by ART deficiency in mice and rats prone to autoimmune diseases (8,24,25).…”

Section: Discussionmentioning

confidence: 58%

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Rapid Induction of Naive T Cell Apoptosis by Ecto-Nicotinamide Adenine Dinucleotide: Requirement for Mono(ADP-Ribosyl)Transferase 2 and a Downstream Effector

Adriouch

Ohlrogge²,

Haag³

et al. 2001

The Journal of Immunology

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Lymphocytes express a number of NAD-metabolizing ectoenzymes, including mono(ADP-ribosyl)transferases (ART) and ADP ribosylcyclases. These enzymes may regulate lymphocyte functions following the release of NAD in injured or inflammatory tissues We report here that extracellular NAD induces apoptosis in BALB/c splenic T cells with an IC50 of 3–5 μM. Annexin V staining of cells was observed already 10 min after treatment with NAD in the absence of any additional signal. Removal of GPI-anchored cell surface proteins by phosphatidylinositol-specific phospholipase C treatment rendered cells resistant to NAD-mediated apoptosis. RT-PCR analyses revealed that resting BALB/c T cells expressed the genes for GPI-anchored ART2.1 and ART2.2 but not ART1. ART2-specific antisera blocked radiolabeling of cell surface proteins with both [32P]NAD and NAD-mediated apoptosis. Further analyses revealed that natural knockout mice for Art2.a (C57BL/6) or Art2.b (NZW) were resistant to NAD-mediated apoptosis. Labeling with [32P]NAD revealed strong cell surface ART activity on T cells of C57BL/6 and little if any activity on cells of NZW mice. T cells of (C57BL/6 × NZW)F1 animals showed strong cell surface ART activity and were very sensitive to NAD-induced apoptosis. As in BALB/c T cells, ART2-specific antisera blocked cell surface ART activity and apoptosis in (C57BL/6 × NZW)F1 T cells. The fact that T cells of F1 animals are sensitive to rapid NAD-induced apoptosis suggests that this effect requires the complementation of (at least) two genetic components. We propose that one of these is cell surface ART2.2 activity (defective in the NZW parent), the other a downstream effector of ADP-ribosylation (defective in the C57BL/6 parent).

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Section: Discussionmentioning

confidence: 58%

“…Indeed, diabetes prone BB-DP rats have reduced ART2 expression, and the transfer of ART2 ϩ T cells from their BB-DR-resistant counterparts confers protection. Failure to develop this T cell subset is thus one of the genetically determined factors leading to enhanced susceptibility for autoimmune diabetes (8).…”

mentioning

confidence: 99%

Rapid Induction of Naive T Cell Apoptosis by Ecto-Nicotinamide Adenine Dinucleotide: Requirement for Mono(ADP-Ribosyl)Transferase 2 and a Downstream Effector

Adriouch

Ohlrogge²,

Haag³

et al. 2001

The Journal of Immunology

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“…Lymphopenia in the BB rat is associated with a marked reduction in blood lymphocytes (Jackson et al 1981;Bellgrau et al 1982;Poussier et al 1982;Elder and Maclaren 1983;Guttmann et al 1983;Plamondon et al 1990;Eastman et al 1991) affecting both CD4 + and CD8 + T cells (Crisá et al 1992), but in particular, T cells with the RT6 (ART2) T-cell marker (Greiner et al 1997). Clearly, the reduction in T cells affects primarily peripheral blood, spleen, and lymph nodes, but not thymus (Gold and Bellgrau 1991;Bieg et al 1997;Hernandez-Hoyos et al 1999).…”

Section: Discussionmentioning

confidence: 99%

Lymphopenia in the BB Rat Model of Type 1 Diabetes is Due to a Mutation in a Novel Immune-Associated Nucleotide (Ian)-Related Gene

MacMurray¹,

Moralejo²,

Kwitek³

et al. 2002

Genome Res.

207

224

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The BB (BioBreeding) rat is one of the best models of spontaneous autoimmune diabetes and is used to study non-MHC loci contributing to Type 1 diabetes. Type 1 diabetes in the diabetes-prone BB (BBDP) rat is polygenic, dependent upon mutations at several loci.Iddm1, on chromosome 4, is responsible for a lymphopenia (lyp) phenotype and is essential to diabetes. In this study, we report the positional cloning of theIddm1/lyp locus. We show that lymphopenia is due to a frameshift deletion in a novel member (Ian5) of the Immune-Associated Nucleotide (IAN)-related gene family, resulting in truncation of a significant portion of the protein. This mutation was absent in 37 other inbred rat strains that are nonlymphopenic and nondiabetic. The IAN gene family, lying within a tight cluster on rat chromosome 4, mouse chromosome 6, and human chromosome 7, is poorly characterized. Some members of the family have been shown to be expressed in mature T cells and switched on during thymic T-cell development, suggesting thatIan5 may be a key factor in T-cell development. The lymphopenia mutation may thus be useful not only to elucidate Type 1 diabetes, but also in the function of the Ian gene family as a whole.[Sequence data reported in this paper has been deposited in GenBank and assigned the following accession nos:AF517674, AF517675, AF517676, and AF517677. Supplemental material is available online at http://depts.washington.edu/rhwlab/ and http:www.genome.org. ] The following individuals and institutions kindly provided reagents, samples, or unpublished information as indicated in the paper: K. Matsumoto and the Sir Frederick Banting Research Centre.

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“…Two-color flow cytometry has revealed that percentages of both RT6.2+CD4+ and RT6.2+CD8+ T lymphocytes decrease on day 15 of mercury treatment (202). Studies of diabetes-prone BB rats have suggested that RT6+ T cells may have a still unexplained immunoregulatory role (211)(212)(213)(214).…”

Section: Mercury-induced Renal Autoimmunitymentioning

confidence: 99%

Metals and Kidney Autoimmunity

Bigazzi¹

1999

Environmental Health Perspectives

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The T Cell Marker RT6 in a Rat Model of Autoimmune Diabetes

Cited by 16 publications

References 33 publications

Rapid Induction of Naive T Cell Apoptosis by Ecto-Nicotinamide Adenine Dinucleotide: Requirement for Mono(ADP-Ribosyl)Transferase 2 and a Downstream Effector

Rapid Induction of Naive T Cell Apoptosis by Ecto-Nicotinamide Adenine Dinucleotide: Requirement for Mono(ADP-Ribosyl)Transferase 2 and a Downstream Effector

Lymphopenia in the BB Rat Model of Type 1 Diabetes is Due to a Mutation in a Novel Immune-Associated Nucleotide (Ian)-Related Gene

Metals and Kidney Autoimmunity

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