Abstract Book 2010 - CIMT Annual Meeting

099 Hemmerling | Tumor biology & interaction with the immune system
Human Langerhans cells reconstitute in skin xenografts
Julia Hemmerling 1 , Joanna Wegner-Kops 1 , Diana Wolff 1 , Maria Sommer 1 , Eva M. Wagner 1 ,
Esther von Stebut 2 , Udo F. Hartwig 1 , Rudolf E. Schopf 2 , Matthias Theobald 1 , Wolfgang
Herr 1 , Ralf G. Meyer 1
1 Department of Hematology/Oncology and
2 Department of Dermatology, at the University Medical Center of the Johannes Gutenberg-University
Mainz, Germany
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Dendritic cells (DC) of the skin, e.g. epidermal Lan-
gerhans cells (LC), are potent regulators of T cells.
They therefore are interesting targets for autologous
T-cell stimulation in the context of vaccinestrategies
as well as for the manipulation of allo-reactive
T-cells in graft-versus-host disease (GVHD).
In an attempt to study the biology of human LC in
vivo, we transplanted human skin to immunodeficient
NOD/SCID/γcnull (NSG) mice and studied the
impact of xeno-transplantation on the distribution
of LC in comparison to that of CD11c positive dermal
DC. We analyzed skin xenografts at different time
points after transplantation and found that during
wound healing, LC were absent in grafts prepared
4 to 6 weeks after transplantation. However, in
many animals analyzed beyond week 6, LC were
again present with almost normal distribution.
These findings were re-confirmed by staining with
antibodies against human CD1a, CD207/Langerin,
S100 and HLA-DR. CD11c positive human dermal
cells were also transiently reduced in numbers, but
never vanished from the dermis after xenografting.
In subsequent experiments, we analyzed the skin
grafts by sequential biopsies and again demonstrated
that more than 50 % of the skin grafts were
devoid of LC in week 6. Three to 5 weeks later,
LC were detected again in these transplants with a
slightly reduced density compared to normal skin.
In congenic mouse models of hematopoietic stem
cell transplantation, murine LC have been shown
to re-populate after local skin injury without the
need of blood-derived precursors. Up to now, there
are only few data supporting this hypothesis for
human LC. By demonstrating the re-establishment
of LC in the xenografts in the absence of any human
hematopoiesis, our data confirm that human LC are
able to re-populate the skin after local depletion.
We further analyzed the proliferative activity of
LC in the xenografts by double staining of CD207/
Langerin-positive cells with Ki67 and found a significantly
increased proliferative activity of LC
compared to healthy skin (31% vs. 5%). Proliferation
is a unique feature of LC among DC. Our data
suggest that this contributes to LC-reconstitution.
In summary, we introduce a human skin xenograftmodel
that allows studying the biology of LC and
dermal DC. Our findings help to unravel the phenomenon
of local LC-reconstitution in human skin.
This model might also help to study the role of skin
DC for inflammatory skin disease and skin GVHD
as well as for vaccine-strategies in vivo.