B7-CD28 interaction promotes proliferation and survival but suppresses differentiation of CD4-CD8- T cells in the thymus

Xincheng Zheng; Jian-Xin Gao; Xing Chang; Yin Wang; Yan Liu; Jing Wen; Huiming Zhang; Jian Zhang; Yang Liu; Pan Zheng

doi:10.4049/jimmunol.173.4.2253

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B7-CD28 interaction promotes proliferation and survival but suppresses differentiation of CD4-CD8- T cells in the thymus

Journal article

Peer reviewed

B7-CD28 interaction promotes proliferation and survival but suppresses differentiation of CD4-CD8- T cells in the thymus

Xincheng Zheng, Jian-Xin Gao, Xing Chang, Yin Wang, Yan Liu, Jing Wen, Huiming Zhang, Jian Zhang, Yang Liu and Pan Zheng

The Journal of immunology (1950), Vol.173(4), pp.2253-2261

08/15/2004

DOI: 10.4049/jimmunol.173.4.2253

PMID: 15294937

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Abstract

Costimulatory molecules play critical roles in the induction and effector function of T cells. More recent studies reveal that costimulatory molecules enhance clonal deletion of autoreactive T cells as well as generation and homeostasis of the CD25(+)CD4(+) regulatory T cells. However, it is unclear whether the costimulatory molecules play any role in the proliferation and differentiation of T cells before they acquire MHC-restricted TCR. In this study, we report that targeted mutations of B7-1 and B7-2 substantially reduce the proliferation and survival of CD4(-)CD8(-) (double-negative (DN)) T cells in the thymus. Perhaps as a result of reduced proliferation, the accumulation of RAG-2 protein in the DN thymocytes is increased in B7-deficient mice, which may explain the increased expression of TCR gene and accelerated transition of CD25(+)CD44(-) (DN3) to CD25(-)CD44(-) (DN4) stage. Qualitatively similar, but quantitatively less striking effects were observed in mice with a targeted mutation of CD28, but not CTLA4. Taken together, our results demonstrate that the development of DN in the thymus is subject to modulation by the B7-CD28 costimulatory pathway.

Flow Cytometry

Immunohistochemistry

Mutation

Antigens, CD - immunology

B7-1 Antigen - genetics

Membrane Glycoproteins - metabolism

Antigens, CD - genetics

Antigens, CD - metabolism

CD28 Antigens - metabolism

DNA-Binding Proteins - metabolism

B7-2 Antigen

Signal Transduction - immunology

CD28 Antigens - genetics

Cell Division - immunology

Membrane Glycoproteins - immunology

Thymus Gland - metabolism

DNA-Binding Proteins - immunology

B7-1 Antigen - immunology

B7-1 Antigen - metabolism

CD28 Antigens - immunology

Cell Survival - immunology

Reverse Transcriptase Polymerase Chain Reaction

Blotting, Western

Membrane Glycoproteins - genetics

Cell Differentiation - immunology

Animals

T-Lymphocytes - cytology

T-Lymphocytes - immunology

Thymus Gland - immunology

Mice

Genes, T-Cell Receptor - immunology

Details

Title: Subtitle: B7-CD28 interaction promotes proliferation and survival but suppresses differentiation of CD4-CD8- T cells in the thymus
Creators: Xincheng Zheng - Division of Cancer Immunology, Department of Pathology, Ohio State University Medical Center and Comprehensive Cancer Center, Columbus, OH 43210, USA
Jian-Xin Gao
Xing Chang
Yin Wang
Yan Liu
Jing Wen
Huiming Zhang
Jian Zhang
Yang Liu
Pan Zheng
Resource Type: Journal article
Publication Details: The Journal of immunology (1950), Vol.173(4), pp.2253-2261
DOI: 10.4049/jimmunol.173.4.2253
PMID: 15294937
NLM abbreviation: J Immunol
ISSN: 0022-1767
eISSN: 1550-6606
Publisher: United States
Grant note: CA58033 / NCI NIH HHS K02 AR049047 / NIAMS NIH HHS P01 AR045652 / NIAMS NIH HHS AI51342 / NIAID NIH HHS
Language: English
Date published: 08/15/2004
Academic Unit: Pathology
Record Identifier: 9984047749602771

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