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The interferon regulatory transcription factor IRF-1 controls positive and negative selection of CD8+ thymocytes

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The interferon regulatory transcription factor IRF-1 controls positive and negative selection of CD8+ thymocytes. / Penninger, J M; Sirard, C; Mittrücker, H W; Chidgey, A; Kozieradzki, I; Nghiem, M; Hakem, A; Kimura, T; Timms, E; Boyd, R; Taniguchi, T; Matsuyama, T; Mak, T W.

In: IMMUNITY, Vol. 7, No. 2, 01.08.1997, p. 243-54.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Penninger, JM, Sirard, C, Mittrücker, HW, Chidgey, A, Kozieradzki, I, Nghiem, M, Hakem, A, Kimura, T, Timms, E, Boyd, R, Taniguchi, T, Matsuyama, T & Mak, TW 1997, 'The interferon regulatory transcription factor IRF-1 controls positive and negative selection of CD8+ thymocytes', IMMUNITY, vol. 7, no. 2, pp. 243-54.

APA

Penninger, J. M., Sirard, C., Mittrücker, H. W., Chidgey, A., Kozieradzki, I., Nghiem, M., Hakem, A., Kimura, T., Timms, E., Boyd, R., Taniguchi, T., Matsuyama, T., & Mak, T. W. (1997). The interferon regulatory transcription factor IRF-1 controls positive and negative selection of CD8+ thymocytes. IMMUNITY, 7(2), 243-54.

Vancouver

Penninger JM, Sirard C, Mittrücker HW, Chidgey A, Kozieradzki I, Nghiem M et al. The interferon regulatory transcription factor IRF-1 controls positive and negative selection of CD8+ thymocytes. IMMUNITY. 1997 Aug 1;7(2):243-54.

Bibtex

@article{979e503ac69943e39d535bbd6aa49881,
title = "The interferon regulatory transcription factor IRF-1 controls positive and negative selection of CD8+ thymocytes",
abstract = "Little is known about the molecular mechanisms and transcriptional regulation that govern T cell selection processes and the differentiation of CD4+ and CD8+ T cells. Mice lacking the interferon regulatory transcription factor-1 (IRF-1) have reduced numbers of mature CD8+ cells within the thymus and peripheral lymphatic organs. Here we show that positive and negative T cell selection of two MHC class I-restricted TCR alphabeta transgenes, H-Y and P14, are impaired in IRF-1-/- mice. The absence of IRF-1 resulted in decreased expression of LMP2, TAP1, and MHC class I on thymic stromal cells. Despite decreased MHC class I expression on IRF-1-/- thymic stromal cells, the defect in CD8+ T cells development did not reside in the thymic environment, and IRF-1-/- stromal cells can fully support development of CD8+ thymocytes in in vivo bone marrow chimeras and in vitro reaggregation cultures. Moreover, IRF-1-/- thymocytes displayed impaired TCR-mediated signal transduction, and the induction of negative selection in TCR Tg thymocytes from IRF-1-/- mice required a 1000-fold increase in selecting peptide. We also provide evidence that IRF-1 is mainly expressed in mature, but not immature, thymocytes and that expression of IRF-1 in immature thymocytes is induced after peptide-specific TCR activation. These results indicate that IRF-1 regulates gene expression in developing thymocytes required for lineage commitment and selection of CD8+ thymocytes.",
keywords = "Animals, CD8-Positive T-Lymphocytes, Cell Differentiation, Clonal Deletion, DNA-Binding Proteins, Epitopes, T-Lymphocyte, Female, H-Y Antigen, Histocompatibility Antigens Class I, Interferon Regulatory Factor-1, L Cells (Cell Line), Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Mice, Transgenic, Peptides, Phosphoproteins, Phosphotyrosine, Receptors, Antigen, T-Cell, alpha-beta, Signal Transduction, Thymus Gland, Transcription Factors",
author = "Penninger, {J M} and C Sirard and Mittr{\"u}cker, {H W} and A Chidgey and I Kozieradzki and M Nghiem and A Hakem and T Kimura and E Timms and R Boyd and T Taniguchi and T Matsuyama and Mak, {T W}",
year = "1997",
month = aug,
day = "1",
language = "English",
volume = "7",
pages = "243--54",
journal = "IMMUNITY",
issn = "1074-7613",
publisher = "Cell Press",
number = "2",

}

RIS

TY - JOUR

T1 - The interferon regulatory transcription factor IRF-1 controls positive and negative selection of CD8+ thymocytes

AU - Penninger, J M

AU - Sirard, C

AU - Mittrücker, H W

AU - Chidgey, A

AU - Kozieradzki, I

AU - Nghiem, M

AU - Hakem, A

AU - Kimura, T

AU - Timms, E

AU - Boyd, R

AU - Taniguchi, T

AU - Matsuyama, T

AU - Mak, T W

PY - 1997/8/1

Y1 - 1997/8/1

N2 - Little is known about the molecular mechanisms and transcriptional regulation that govern T cell selection processes and the differentiation of CD4+ and CD8+ T cells. Mice lacking the interferon regulatory transcription factor-1 (IRF-1) have reduced numbers of mature CD8+ cells within the thymus and peripheral lymphatic organs. Here we show that positive and negative T cell selection of two MHC class I-restricted TCR alphabeta transgenes, H-Y and P14, are impaired in IRF-1-/- mice. The absence of IRF-1 resulted in decreased expression of LMP2, TAP1, and MHC class I on thymic stromal cells. Despite decreased MHC class I expression on IRF-1-/- thymic stromal cells, the defect in CD8+ T cells development did not reside in the thymic environment, and IRF-1-/- stromal cells can fully support development of CD8+ thymocytes in in vivo bone marrow chimeras and in vitro reaggregation cultures. Moreover, IRF-1-/- thymocytes displayed impaired TCR-mediated signal transduction, and the induction of negative selection in TCR Tg thymocytes from IRF-1-/- mice required a 1000-fold increase in selecting peptide. We also provide evidence that IRF-1 is mainly expressed in mature, but not immature, thymocytes and that expression of IRF-1 in immature thymocytes is induced after peptide-specific TCR activation. These results indicate that IRF-1 regulates gene expression in developing thymocytes required for lineage commitment and selection of CD8+ thymocytes.

AB - Little is known about the molecular mechanisms and transcriptional regulation that govern T cell selection processes and the differentiation of CD4+ and CD8+ T cells. Mice lacking the interferon regulatory transcription factor-1 (IRF-1) have reduced numbers of mature CD8+ cells within the thymus and peripheral lymphatic organs. Here we show that positive and negative T cell selection of two MHC class I-restricted TCR alphabeta transgenes, H-Y and P14, are impaired in IRF-1-/- mice. The absence of IRF-1 resulted in decreased expression of LMP2, TAP1, and MHC class I on thymic stromal cells. Despite decreased MHC class I expression on IRF-1-/- thymic stromal cells, the defect in CD8+ T cells development did not reside in the thymic environment, and IRF-1-/- stromal cells can fully support development of CD8+ thymocytes in in vivo bone marrow chimeras and in vitro reaggregation cultures. Moreover, IRF-1-/- thymocytes displayed impaired TCR-mediated signal transduction, and the induction of negative selection in TCR Tg thymocytes from IRF-1-/- mice required a 1000-fold increase in selecting peptide. We also provide evidence that IRF-1 is mainly expressed in mature, but not immature, thymocytes and that expression of IRF-1 in immature thymocytes is induced after peptide-specific TCR activation. These results indicate that IRF-1 regulates gene expression in developing thymocytes required for lineage commitment and selection of CD8+ thymocytes.

KW - Animals

KW - CD8-Positive T-Lymphocytes

KW - Cell Differentiation

KW - Clonal Deletion

KW - DNA-Binding Proteins

KW - Epitopes, T-Lymphocyte

KW - Female

KW - H-Y Antigen

KW - Histocompatibility Antigens Class I

KW - Interferon Regulatory Factor-1

KW - L Cells (Cell Line)

KW - Male

KW - Mice

KW - Mice, Inbred C57BL

KW - Mice, Knockout

KW - Mice, Transgenic

KW - Peptides

KW - Phosphoproteins

KW - Phosphotyrosine

KW - Receptors, Antigen, T-Cell, alpha-beta

KW - Signal Transduction

KW - Thymus Gland

KW - Transcription Factors

M3 - SCORING: Journal article

C2 - 9285409

VL - 7

SP - 243

EP - 254

JO - IMMUNITY

JF - IMMUNITY

SN - 1074-7613

IS - 2

ER -