Abstracts (complete list) - Wissenschaft Online

Sabine Ring, Karsten Mahnke, Alexander Enk
In vivo activation of injected Tregs precedes the suppression
of the elicitation phase of Contact hypersensitivity reactions
independent from spleen and lymph nodes
We previously demonstrated that adoptively transferred naïve CD4+CD25+ T cells
(Treg) suppress the elicitation phase of allergic contact dermatitis (CHS), by inhibiting
the endothelium-interaction and extravasation of effector CD8+ T cells.
Since activation of Treg is necessary to generate this suppressive activity, we
determined the activation status of isolated Tregs in the course of injection. Directly
after isolation, the naïve CD4+CD25+ T cells displayed a non-activated phenotype as
assessed by low expression of CD69 and CD44, and high expression of CD62L. 2h after
injection and re-isolation of the dye-labelled Treg we detected significantly increased
expression of the activation markers CD69, Foxp3 and CD44, whereas CD62L decreased
in Treg in vivo after hapten application. This indicates that Treg become activated in
vivo after injection and explains the comparable suppressive function of naïve and
activated Treg in vivo. To further determine the importance of homing to lymphoid
organs for Treg action, we splenektomised mice or injected CD62L- Treg. By this way
we excluded the homing of Treg to spleen or lymph nodes, respectively. In these
experiments the Treg were still able to suppress the elicitation phase of CHS, indicating
that peripheral lymphoid organs are not essential for the activation and consequently
for the suppressive capacity of injected naïve Treg in vivo.
These data show that naïve Treg upregulate characteristic activation markers in vivo
after hapten application which results in the suppression of the elicitation phase of CHS,
independently of peripheral lymphoid organs. Therefore we can speculate that cellular
interaction(s) in the blood or at the site of inflammation and/or soluble factors are
involved in mediating suppressive function(s) of Treg in a CHS model.