Abstracts (complete list) - Wissenschaft Online

Nils Kruse, Arnhild Schrage, Katrin Neumann, Katharina Eulenburg, Friderike
Blumenthal-Barby, Simon Fillatreau, Percy A. Knolle, Martin Zeitz, Alf Hamann, Katja
Klugewitz
Naive CD4+ T cells primed by Liver Sinusoidal Endothelial
Cells (LSEC) do not differentiate into cytokine producing
effector cells and fail to induce a delayed type
hypersensitivity reaction (DTH)
The liver, which is known to have immunomodulatory functions, favours the induction of
tolerance rather than immunity. For example LSEC, one population of hepatic nonprofessional
antigen presenting cells (APC) prime CD8 + T cells leading to anergy or
deletion. But it is controversial if LSEC can prime naive CD4 + T cells. Whereas LSEC
isolated by counterflow elutriation primed naive CD4 + T cells, others have reported that
LSEC isolated by depletion of CD45 + cells were not sufficient to induce proliferation of
naive CD4 + T cells.
In our study we investigated if naïve CD4 + T cells can be primed by LSEC alone by
using a novel experimental approach. To exclude the influence of professional APC, we
immunomagnetically purified LSEC from bone marrow chimeric mice that express MHC
class II exclusively on non-hematopoietic cells. We analyzed the phenotype and the
functional properties of the LSEC primed CD4 + T cells.
We demonstrated that LSEC alone can prime naive CD4 + T cells in vitro, determined by
proliferation. However the LSEC were weak presenters, as high antigen concentrations
were required. The CD4 + T cells neither differentiated into IFNγ expressing Th1 cells nor
produced IL-4 or IL-10. In an in vitro suppression assay this T cell population
suppressed the proliferation of naive CD4 + T cells. But markers characteristic for
regulatory T cells (CD25, Foxp3 and αE) were negligible. Concerning their
proinflammatory capacity LSEC primed CD4 + T cells did not induce a DTH reaction in
contrast to CD4 + T cells primed by professional APC. Determining the stability of their
phenotype in vivo we observed that the cells did not express IFNγ after transfer into
syngeneic mice, even in the presence of the specific antigen.
Taken together CD4 + T cells can be primed by LSEC and acquire an anergic phenotype.
This modulation might be involved in establishing and maintaining hepatic tolerance not
only for CD8 + T cells but also for CD4 + T cells.