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Thymocyte glucocorticoid resistance alters positive selection and inhibits autoimmunity and lymphoproliferative disease in MRL-lpr/lpr mice

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Thymocyte glucocorticoid resistance alters positive selection and inhibits autoimmunity and lymphoproliferative disease in MRL-lpr/lpr mice. / Tolosa, E; King, L B; Ashwell, J D.

in: IMMUNITY, Jahrgang 8, Nr. 1, 01.01.1998, S. 67-76.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Tolosa, E, King, LB & Ashwell, JD 1998, 'Thymocyte glucocorticoid resistance alters positive selection and inhibits autoimmunity and lymphoproliferative disease in MRL-lpr/lpr mice', IMMUNITY, Jg. 8, Nr. 1, S. 67-76.

APA

Tolosa, E., King, L. B., & Ashwell, J. D. (1998). Thymocyte glucocorticoid resistance alters positive selection and inhibits autoimmunity and lymphoproliferative disease in MRL-lpr/lpr mice. IMMUNITY, 8(1), 67-76.

Vancouver

Tolosa E, King LB, Ashwell JD. Thymocyte glucocorticoid resistance alters positive selection and inhibits autoimmunity and lymphoproliferative disease in MRL-lpr/lpr mice. IMMUNITY. 1998 Jan 1;8(1):67-76.

Bibtex

@article{d9ffffef42ca4feca138e889ad0112a7,
title = "Thymocyte glucocorticoid resistance alters positive selection and inhibits autoimmunity and lymphoproliferative disease in MRL-lpr/lpr mice",
abstract = "Thymus-derived glucocorticoids antagonize T cell receptor (TCR)-induced thymocyte apoptosis, allowing the survival (positive selection) of cells bearing TCRs that recognize self antigens with low-to-moderate avidity. Here we demonstrate that expression of an antisense glucocorticoid receptor transgene in thymocytes of spontaneously autoimmune MRL-lpr/lpr mice causes the loss of specific TCR Vbeta-bearing T cells that are normally positively selected in this strain. These transgenic mice had lower autoantibody production and milder symptoms of autoimmune disease than MRL-lpr/lpr controls and had markedly reduced accumulation of the TCR+Thy-1+CD4-CD8-B220+ T cells that are the hallmark of the lpr mutation. Thus, decreased glucocorticoid signaling in thymocytes alters the T cell repertoire and greatly diminishes autoimmunity in MRL-lpr/lpr autoimmune mice.",
keywords = "Animals, Apoptosis, Autoantibodies, Autoimmunity, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Cell Survival, DNA, DNA, Antisense, Gene Expression, Glomerulonephritis, Lymphocyte Activation, Lymphoproliferative Disorders, Mice, Mice, Transgenic, Mitogens, Receptors, Antigen, T-Cell, Receptors, Glucocorticoid, Stimulation, Chemical, Thymus Gland, Transgenes",
author = "E Tolosa and King, {L B} and Ashwell, {J D}",
year = "1998",
month = jan,
day = "1",
language = "English",
volume = "8",
pages = "67--76",
journal = "IMMUNITY",
issn = "1074-7613",
publisher = "Cell Press",
number = "1",

}

RIS

TY - JOUR

T1 - Thymocyte glucocorticoid resistance alters positive selection and inhibits autoimmunity and lymphoproliferative disease in MRL-lpr/lpr mice

AU - Tolosa, E

AU - King, L B

AU - Ashwell, J D

PY - 1998/1/1

Y1 - 1998/1/1

N2 - Thymus-derived glucocorticoids antagonize T cell receptor (TCR)-induced thymocyte apoptosis, allowing the survival (positive selection) of cells bearing TCRs that recognize self antigens with low-to-moderate avidity. Here we demonstrate that expression of an antisense glucocorticoid receptor transgene in thymocytes of spontaneously autoimmune MRL-lpr/lpr mice causes the loss of specific TCR Vbeta-bearing T cells that are normally positively selected in this strain. These transgenic mice had lower autoantibody production and milder symptoms of autoimmune disease than MRL-lpr/lpr controls and had markedly reduced accumulation of the TCR+Thy-1+CD4-CD8-B220+ T cells that are the hallmark of the lpr mutation. Thus, decreased glucocorticoid signaling in thymocytes alters the T cell repertoire and greatly diminishes autoimmunity in MRL-lpr/lpr autoimmune mice.

AB - Thymus-derived glucocorticoids antagonize T cell receptor (TCR)-induced thymocyte apoptosis, allowing the survival (positive selection) of cells bearing TCRs that recognize self antigens with low-to-moderate avidity. Here we demonstrate that expression of an antisense glucocorticoid receptor transgene in thymocytes of spontaneously autoimmune MRL-lpr/lpr mice causes the loss of specific TCR Vbeta-bearing T cells that are normally positively selected in this strain. These transgenic mice had lower autoantibody production and milder symptoms of autoimmune disease than MRL-lpr/lpr controls and had markedly reduced accumulation of the TCR+Thy-1+CD4-CD8-B220+ T cells that are the hallmark of the lpr mutation. Thus, decreased glucocorticoid signaling in thymocytes alters the T cell repertoire and greatly diminishes autoimmunity in MRL-lpr/lpr autoimmune mice.

KW - Animals

KW - Apoptosis

KW - Autoantibodies

KW - Autoimmunity

KW - CD4-Positive T-Lymphocytes

KW - CD8-Positive T-Lymphocytes

KW - Cell Survival

KW - DNA

KW - DNA, Antisense

KW - Gene Expression

KW - Glomerulonephritis

KW - Lymphocyte Activation

KW - Lymphoproliferative Disorders

KW - Mice

KW - Mice, Transgenic

KW - Mitogens

KW - Receptors, Antigen, T-Cell

KW - Receptors, Glucocorticoid

KW - Stimulation, Chemical

KW - Thymus Gland

KW - Transgenes

M3 - SCORING: Journal article

C2 - 9462512

VL - 8

SP - 67

EP - 76

JO - IMMUNITY

JF - IMMUNITY

SN - 1074-7613

IS - 1

ER -