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  - Langenhorst, Daniela
A1  - Gogishvili, Tea
A1  - Ribechini, Eliana
A1  - Kneitz, Susanne
A1  - McPherson, Kirsty
A1  - Lutz, Manfred B.
A1  - Hünig, Thomas
T1  - Sequential induction of effector function, tissue migration and cell death during polyclonal activation of mouse regulatory T-cells
N2  - The ability of CD4+Foxp3+ regulatory T-cells (Treg) to produce interleukin (IL)-10 is important for the limitation of inflammation at environmental interfaces like colon or lung. Under steady state conditions, however, few Tregs produce IL-10 ex vivo. To investigate the origin and fate of IL-10 producing Tregs we used a superagonistic mouse anti-mouse CD28 mAb (CD28SA) for polyclonal in vivo stimulation of Tregs, which not only led to their numeric expansion but also to a dramatic increase in IL-10 production. IL-10 secreting Tregs strongly upregulated surface receptors associated with suppressive function as compared to non-producing Tregs. Furthermore, polyclonally expanding Tregs shifted their migration receptor pattern after activation from a CCR7+CCR52 lymph node-seeking to a CCR72CCR5+ inflammationseeking phenotype, explaining the preferential recruitment of IL-10 producers to sites of ongoing immune responses. Finally, we observed that IL-10 producing Tregs from CD28SA stimulated mice were more apoptosis-prone in vitro than their IL-10 negative counterparts. These findings support a model where prolonged activation of Tregs results in terminal differentiation towards an IL-10 producing effector phenotype associated with a limited lifespan, implicating built-in termination of immunosuppression.
KW  - Medizin
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-76009
ER  -