Suppressive mechanisms of regulatory T cells controlling CD8+ T cells in steady state, cancer and chronic infection

Abstract:

Suppression of CD8+ T cells by CD4+ FoxP3+ regulatory T cells (Treg) protects the organism from excessive immunopathology by CTL in autoimmunity and chronic virus infection but can be exploited by cancer and chronic virus infections to escape immune control. We will use a transgenic mouse model where Treg selectively lack certain effector molecules to identify the mechanisms Treg use to suppress CD8+ T cells in peripheral tolerance, cancer and chronic viral infection.

Principal investigators:

Dr. sc. nat. Hans Christian Probst
Institut für Immunologie
Universitätsmedizin der Johannes Gutenberg-Universität Mainz
Langenbeckstraße 1, 55131 Mainz
Phone +49 (0)6131 17-6174
E-Mail: hcprobst@uni-mainz.de
Web: http://www.unimedizin-mainz.de/immunology/laboratories/probst-laboratory.html?L=1

Univ.-Prof. Dr. rer. physiol. Hansjörg Schild
Institut für Immunologie
Universitätsmedizin der Johannes Gutenberg-Universität Mainz
Langenbeckstraße 1, 55131 Mainz
Phone +49 (0)6131 17-6198
E-Mail: schild@uni-mainz.de
Web: http://www.unimedizin-mainz.de/immunology/team/further-information/schild.html?L=1

Postdoc:

Dr. Sabine Muth

Doctoral candidate:

Mona Grans

Project-related publications:

Muth S, Schütze K, Hain T, Yagita H, Schild H & H. C. Probst (2014) A CD40/CD40L feedback loop drives the breakdown of CD8 T-cell tolerance following depletion of suppressive CD4 T cells. Eur J Immunol 44:1099-107

Probst HC, Muth S & Schild H (2014) Regulation of the tolerogenic function of steady-state DCs. Eur J Immunol 44:927-933

Muth S, Schutze K, Schild H & Probst HC (2012) Release of dendritic cells from cognate CD4+ T-cell recognition results in impaired peripheral tolerance and fatal cytotoxic T-cell mediated autoimmunity. Proc Natl Acad Sci U S A 109:9059-9064

Gupta A, Probst HC, Vuong V, Landshammer A, Muth S, Yagita H, Schwendener R, Pruschy M, Knuth A & van den Broek M (2012) Radiotherapy Promotes Tumor-Specific Effector CD8+ T Cells via Dendritic Cell Activation. J Immunol 189:558-566

Stein P, Rechtsteiner G, Warger T, Bopp T, Fuhr T, Prufer S, Probst HC, Stassen M, Langguth P, Schild H & Radsak MP. 2011. UV exposure boosts transcutaneous immunization and improves tumor immunity: cytotoxic T-cell priming through the skin. J Invest Dermatol 131:211-219

Schildknecht A, Brauer S, Brenner C, Lahl K, Schild H, Sparwasser T* & Probst HC*, van den Broek M* (2010) FoxP3+ regulatory T cells essentially contribute to peripheral CD8+ T-cell tolerance induced by steady-state dendritic cells. Proc Natl Acad Sci U S A 107:199-203. (*joint senior authors)

Fassbender M, Gerlitzki B, Ullrich N, Lupp C, Klein M, Radsak MP, Schmitt E, Bopp T & Schild H (2010) Cyclic adenosine monophosphate and IL-10 coordinately contribute to nTreg cell-mediated suppression of dendritic cell activation. Cell Immunol 265:91-96.

Probst HC, McCoy K, Okazaki T, Honjo T & van den Broek M (2005) Resting dendritic cells induce peripheral CD8+ T cell tolerance through PD-1 and CTLA-4. Nat Immunol 6:280-286

Probst HC, Lagnel J, Kollias G & van den Broek M (2003) Inducible transgenic mice reveal resting dendritic cells as potent inducers of CD8+ T cell tolerance. Immunity 18:713-720