The kidney-renal lymph node-system contributes to cross-tolerance against innocuous circulating antigen

TY - JOUR

T1 - The kidney-renal lymph node-system contributes to cross-tolerance against innocuous circulating antigen

AU - Lukacs-Kornek, Veronika

AU - Burgdorf, Sven

AU - Diehl, Linda

AU - Specht, Sabine

AU - Kornek, Miroslaw

AU - Kurts, Christian

PY - 2008/1/15

Y1 - 2008/1/15

N2 - Soluble Ags devoid of inflammatory stimuli, derived for example from self-serum or food proteins, induce T cell tolerance, predominantly in the spleen. In this study, we describe an additional role of the kidney-renal LN (rLN) system in tolerogenic presentation of circulating soluble Ags. Protein below albumin molecular mass constitutively passed the kidney glomerular filter and was concentrated in the tubular compartment. Enriched filterable Ag was endocytosed by kidney dendritic cells (kDCs). Simultaneously, it was transported cell independently within 2 min to DCs resident in rLNs. These DC phenotypically differed from kDCs carrying filterable Ag, and used a distinct mechanism, mannose receptor-mediated endocytosis, to internalize Ag. They activated specific CD8+ T cells, which subsequently proliferated without producing effector cytokines or developing cytotoxic activity, showed a curtailed lifespan and signs of apoptosis. Such T cell tolerization was independent of steady-state migratory kDC, because it occurred also when nephrectomy was performed soon after Ag injection. These findings demonstrate that the kidney dispatches concentrated blood-borne Ags to the rLNs, where they are captured by resident DCs, resulting in CD8+ T cell cross-tolerance. This mechanism may contribute to avoiding immunity against innocuous circulating protein Ags below albumin size.

AB - Soluble Ags devoid of inflammatory stimuli, derived for example from self-serum or food proteins, induce T cell tolerance, predominantly in the spleen. In this study, we describe an additional role of the kidney-renal LN (rLN) system in tolerogenic presentation of circulating soluble Ags. Protein below albumin molecular mass constitutively passed the kidney glomerular filter and was concentrated in the tubular compartment. Enriched filterable Ag was endocytosed by kidney dendritic cells (kDCs). Simultaneously, it was transported cell independently within 2 min to DCs resident in rLNs. These DC phenotypically differed from kDCs carrying filterable Ag, and used a distinct mechanism, mannose receptor-mediated endocytosis, to internalize Ag. They activated specific CD8+ T cells, which subsequently proliferated without producing effector cytokines or developing cytotoxic activity, showed a curtailed lifespan and signs of apoptosis. Such T cell tolerization was independent of steady-state migratory kDC, because it occurred also when nephrectomy was performed soon after Ag injection. These findings demonstrate that the kidney dispatches concentrated blood-borne Ags to the rLNs, where they are captured by resident DCs, resulting in CD8+ T cell cross-tolerance. This mechanism may contribute to avoiding immunity against innocuous circulating protein Ags below albumin size.

KW - Animals

KW - Antigens

KW - CD8-Positive T-Lymphocytes

KW - Cross-Priming

KW - Dendritic Cells

KW - Endocytosis

KW - Immune Tolerance

KW - Kidney

KW - Lymph Nodes

KW - Lymphocyte Activation

KW - Mice

KW - Ovalbumin

M3 - SCORING: Journal article

C2 - 18178808

VL - 180

SP - 706

EP - 715

JO - J IMMUNOL

JF - J IMMUNOL

SN - 0022-1767

IS - 2

ER -