TY  - JOUR
A1  - Reuter, Dajana
A1  - Sparwasser, Tim
A1  - Hünig, Thomas
A1  - Schneider-Schaulies, Jürgen
T1  - Foxp3\(^+\) Regulatory T Cells Control Persistence of Viral CNS Infection
JF  - PLoS One
N2  - We earlier established a model of a persistent viral CNS infection using two week old immunologically normal (genetically unmodified) mice and recombinant measles virus (MV). Using this model infection we investigated the role of regulatory T cells (Tregs) as regulators of the immune response in the brain, and assessed whether the persistent CNS infection can be modulated by manipulation of Tregs in the periphery. CD4\(^+\) CD25\(^+\) Foxp3\(^+\) Tregs were expanded or depleted during the persistent phase of the CNS infection, and the consequences for the virus-specific immune response and the extent of persistent infection were analyzed. Virus-specific CD8\(^+\) T cells predominantly recognising the H-2D(b)-presented viral hemagglutinin epitope MV-H22-30 (RIVINREHL) were quantified in the brain by pentamer staining. Expansion of Tregs after intraperitoneal (i.p.) application of the superagonistic anti-CD28 antibody D665 inducing transient immunosuppression caused increased virus replication and spread in the CNS. In contrast, depletion of Tregs using diphtheria toxin (DT) in DEREG (depletion of regulatory T cells)-mice induced an increase of virus-specific CD8\(^+\) effector T cells in the brain and caused a reduction of the persistent infection. These data indicate that manipulation of Tregs in the periphery can be utilized to regulate virus persistence in the CNS.
KW  - antigen presentation
KW  - brain
KW  - central-nervous-system
KW  - virus-induced encephalitis
KW  - retroviral infection
KW  - gamma-interferon
KW  - measles virus
KW  - subacute sclerosing-panencephalitis
KW  - mice
KW  - CD4(+)
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-134248
VL  - 7
IS  - 3
ER  - 
TY  - JOUR
A1  - Kühlhorn, Franziska
A1  - Rath, Matthias
A1  - Schmoeckel, Katrin
A1  - Cziupka, Katharina
A1  - Nguyen, Huu Hung
A1  - Hildebrandt, Petra
A1  - Hünig, Thomas
A1  - Sparwasser, Tim
A1  - Huehn, Jochen
A1  - Pötschke, Christian
A1  - Bröker, Barbara M.
T1  - \(Foxp3^+\) Regulatory T Cells Are Required for Recovery from Severe Sepsis
JF  - PLoS ONE
N2  - The role of regulatory T cells (Tregs) in bacterial sepsis remains controversial because antibody-mediated depletion experiments gave conflicting results. We employed DEREG mice (DEpletion of REGulatory T cells) and a caecal ligation and puncture model to elucidate the role of \(CD4^+Foxp3^+\) Tregs in sepsis. In DEREG mice natural Tregs can be visualized easily and selectively depleted by diphtheria toxin because the animals express the diphtheria toxin receptor and enhanced green fluorescent protein as a fusion protein under the control of the foxp3 locus. We confirmed rapid Treg-activation and an increased ratio of Tregs to Teffs in sepsis. Nevertheless, 24 h after sepsis induction, Treg-depleted and control mice showed equally strong inflammation, immune cell immigration into the peritoneum and bacterial dissemination. During the first 36 h of disease survival was not influenced by Treg-depletion. Later, however, only Treg-competent animals recovered from the insult. We conclude that the suppressive capacity of Tregs is not sufficient to control overwhelming inflammation and early mortality, but is a prerequisite for the recovery from severe sepsis.
KW  - CD4(+)CD25(+)
KW  - toll-like receptors
KW  - TGF-BETA
KW  - mediated suppression
KW  - polymicrobial sepsis
KW  - improves survival
KW  - adoptive transfer
KW  - infected mice
KW  - in-vivo
KW  - CD4(+)
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-130940
VL  - 8
IS  - 5
ER  -