1.Maintenance of CD8+T-cell anergy by CD4+CD25+ regulatory T cells in chronic graft-versus-host disease.
Juyang KIM ; Hye J KIM ; Woon S CHOI ; Seok H NAM ; Hong R CHO ; Byungsuk KWON
Experimental & Molecular Medicine 2006;38(5):494-501
In a murine model of systemic lupus erythematosus (SLE)-like chronic graft-versus-host disease (cGVHD), donor CD8+T cells rapidly fall into anergy to host cells, while donor CD4+T cells hyperactivate B cells and break B-cell tolerance to self-Ags in the recipient mouse. The functional recovery of donor CD8+T cells can result in the conversion of cGVHD to acute GVHD (aGVHD), indicating that donor CD8+T-cell anergy is a restriction factor in the development of cGVHD. In this report, we present evidence that donor CD4+CD25+regulatory T cells (T(reg) cells) are critical in maintaining the donor CD8+T-cell anergy and thus suppressing the development of aGVHD in mice that are naturally prone to cGVHD. Our results provide a novel insight into the role of T(reg) cells in determining cGVHD versus aGVHD.
T-Lymphocytes, Regulatory/*immunology
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Mice, Inbred DBA
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Mice
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Interleukin-2 Receptor alpha Subunit/*metabolism
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Immune Tolerance/physiology
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Graft vs Host Disease/*immunology
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Female
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Clonal Anergy/*physiology
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Chronic Disease
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CD8-Positive T-Lymphocytes/*immunology
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CD4-Positive T-Lymphocytes/*immunology
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Animals
2.Differential susceptibility of naïve versus cloned CD4+ T cells to antigen-specific and MHC-restricted anergy induction.
Quan-Sheng LIU ; Rui-Hua ZHANG ; Yi-Wei CHU ; Si-Dong XIONG
Acta Physiologica Sinica 2003;55(6):633-640
T cell anergy has been successfully induced under different conditions in cloned CD4(+) T cells, but induction of T cell anergy in vivo has been difficult and controversial. Due to the low frequency of naturally occurring T cell population with specificity to a defined antigen, it is very difficult to study anergy of naïve T cells without prior in vivo priming which complicates the interpretation of experimental data. To solve this problem, we adopted the HNT-TCR transgenic mice which have homogeneous antigen specific CD4(+) T cell population. In this study, we generated an influenza virus hemagglutinin (HA) peptide-specific CD4(+) T cell clone from the HNT-TCR transgenic mice and induced anergy using APCs which were treated with the crosslinker, ECDI (1-ethyl-3-3(3-dimethylaminopropyl) carbodiimide). The proliferative response of the cloned or freshly purified naïve CD4(+) transgenic T cells after treatment with ECDI-treated APCs and the HA peptide antigen was monitored as the index of anergy induction. The results showed that anergy was successfully induced in the cloned HNT-TCR transgenic CD4(+) T cells. It was determined that the induced anergy was antigen- and MHC-specific. By contrast, anergy was not observed in freshly purified naïve CD4(+) transgenic T cells under the same conditions. The results suggest that naïve CD4(+) T cells may have different anergy inducing requirements, or that cloned CD4(+) T cells may have certain priming or in vitro cloning artifact which makes them more susceptible to anergy induction. We propose that induction of T cell anergy may depend on the T cell growth, activation and differentiation state or cloning conditions. The results from the present study may have important implications for the study of the mechanism(s) underlying T cell anergy induction in vivo and for applications of immune tolerance based therapy.
Animals
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Antigen-Presenting Cells
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immunology
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metabolism
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Antigens, CD
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genetics
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immunology
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metabolism
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CD4 Antigens
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immunology
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CD4-Positive T-Lymphocytes
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cytology
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immunology
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Clonal Anergy
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genetics
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immunology
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Clone Cells
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immunology
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Epitopes, T-Lymphocyte
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biosynthesis
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Immune Tolerance
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genetics
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Major Histocompatibility Complex
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immunology
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Mice
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Mice, Transgenic
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Receptors, Antigen, T-Cell
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physiology