Abstracts (complete list) - Wissenschaft Online

Veronika Lukacs-Kornek, Sven Burgdorf, Sabine Specht, Miroslaw Kornek, Christian
Kurts
The kidney – renal LN system contributes to cross-tolerance
against innocuous soluble antigen
Soluble antigens devoid of inflammatory stimuli, derived for example from self-serum or
food proteins, induce T cell tolerance in the spleen. Here we describe an additional role
of the kidney – rLN system in tolerogenic presentation of such circulating antigens.
Protein below albumin molecular weight constitutively passed the kidney glomerular
filter and was concentrated in the tubular compartment. Enriched filtrated antigen was
endocytosed by kidney dendritic cells (kDC). Simultaneously, it was transported cellindependently
within two minutes to DC resident in rLNs. These DC phenotypically
differed from kDC carrying filtrated antigen, and used a different mechanism, MRmediated
endocytosis, to internalize antigen. They activated specific CD8+ T cells,
which subsequently proliferated without producing effector cytokines or developing
cytotoxic activity, and showed a curtailed life-span. Such tolerogenic T cell activation
was independent of steady-state migratory kidney DC because nephrectomy after
antigen injection did not change the T cell response. These findings demonstrate that
the kidney dispatches concentrated blood-borne antigens to the rLNs, where they can
be captured by resident DC, resulting in tolerogenic CD8+ T cell activation. This
mechanism may contribute to T cell cross-tolerance against innocuous circulating
protein antigens.