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Antigen-specific Treg impair CD8(+) T-cell priming by blocking early T-cell expansion.

Chappert, P; Leboeuf, M; Rameau, P; Lalfer, M; Desbois, S; Liblau, RS; Danos, O; ... Gross, D-A; + view all (2010) Antigen-specific Treg impair CD8(+) T-cell priming by blocking early T-cell expansion. Eur J Immunol , 40 (2) pp. 339-350. 10.1002/eji.200839107.

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Abstract

Foxp3(+) Treg are crucial for the maintenance of self-tolerance and have been shown to control CD8(+) T-cell effector functions. In addition, Treg are thought to control the priming of CD8(+) T cells, which recognize the same antigens as Treg. Taking advantage of our model of peripheral tolerance induction to influenza hemagglutinin (HA) after HA gene transfer, we found that HA-specific Treg suppress antigen-linked CTL responses through early blockade of CD8(+) T-cell expansion. Confronted with their cognate antigen, Treg expand more rapidly than CD8(+) T cells and are highly suppressive only during the initial stages of immune priming. They nullify HA-specific CD8(+) T-cell responses, local inflammatory responses and rejection of HA transduced cells. When HA gene transfer is performed with extensive tissue inflammation, HA-specific Treg are less effective but still reduce the frequency of newly primed HA-specific CD8(+) T cells and the ensuing frequency of memory CD8(+) T cells. Our results demonstrate that Treg control CTL priming in an antigen-specific manner at the level of T-cell expansion, highlighting how self-reactive Treg could prevent the induction of autoimmune responses through selective blockade of autoreactive T-cell proliferation.

Type: Article
Title: Antigen-specific Treg impair CD8(+) T-cell priming by blocking early T-cell expansion.
Location: Germany
DOI: 10.1002/eji.200839107
Keywords: Animals, Antigens, CD8-Positive T-Lymphocytes, Cell Differentiation, Cell Proliferation, Female, Flow Cytometry, H-2 Antigens, Hemagglutinin Glycoproteins, Influenza Virus, Histocompatibility Antigen H-2D, Immunologic Memory, Male, Mice, Mice, Inbred BALB C, Mice, Transgenic, T-Lymphocytes, Cytotoxic, T-Lymphocytes, Regulatory
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Haematology
URI: http://discovery.ucl.ac.uk/id/eprint/90936
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