It is well established that the NOD mouse develops T-cell-dependent autoimmune type I diabetes that is abolished by neonatal Tx and enhanced by Tx at weaning. In a previous study, we demonstrated that the NOD thymus displays various abnormalities in the microenvironmental compartment, including abnormal distribution of epithelial cell subsets, precocious decline in thymic hormone production and formation of giant PVS. These latter structures present an internal ECM-containing network filled with T-cells and to a lesser extent B-cells. Herein we have investigated further the giant PVS and particularly the origin of the T-cells that colonize these structures. The thymic origin of intra-PVS T-cells was ascertained by distinct protocols. First, sublethal X-ray irradiation or HC treatment leading to cortical thymocyte depletion showed that intra-PVS lymphocytes were resistant, similar to medullary thymocytes. Second, adoptive transfer experiments that used newborn or adult irradiated Thy-1 congenic recipients demonstrated that intra-PVS accumulation of T-cells did not result from the reentry of peripheral mature T-cells into the thymus. Third, kinetic studies that used BrdUrd pulse chase revealed that labeled intra-PVS cells appear late, simultaneously with medullary thymocytes, and remain only transiently within the PVS. Thus, the kinetics of T-cell reconstitution of PVS was compatible with the progressive differentiation of T-cell precursors originating from the thymic cortex. In this respect, thegiant PVS of the NOD mouse thymus may represent a useful model to study the relationships between trafficking thymocytes and ECM proteins.
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Original Articles|
January 01 1993
Characterization of the Extracellular Matrix—Containing Giant Perivascular Spaces in the NOD Mouse Thymus Free
Wilson Savino;
Wilson Savino
Department of Immunology, Institute Oswaldo Cruz, Rio de Janeiro
Brazil
Hfipital Necker, INSERM U 25
Paris
CNRS URA 1461
Paris, France
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Claude Carnaud;
Claude Carnaud
Department of Immunology, Institute Oswaldo Cruz, Rio de Janeiro
Brazil
Hfipital Necker, INSERM U 25
Paris
CNRS URA 1461
Paris, France
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Jian-Jian Luan;
Jian-Jian Luan
Department of Immunology, Institute Oswaldo Cruz, Rio de Janeiro
Brazil
Hfipital Necker, INSERM U 25
Paris
CNRS URA 1461
Paris, France
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Jean-François Bach;
Jean-François Bach
Department of Immunology, Institute Oswaldo Cruz, Rio de Janeiro
Brazil
Hfipital Necker, INSERM U 25
Paris
CNRS URA 1461
Paris, France
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Mireille Dardenne
Mireille Dardenne
Department of Immunology, Institute Oswaldo Cruz, Rio de Janeiro
Brazil
Hfipital Necker, INSERM U 25
Paris
CNRS URA 1461
Paris, France
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Address correspondence and reprint requests to Mireille Dardenne, CNRS URA 1461-Hôpital Necker, 161, rue de Sevres, 75743 Paris Cedex 15, France.
Diabetes 1993;42(1):134–140
Article history
Received:
July 06 1992
Revision Received:
August 20 1992
Accepted:
August 20 1992
PubMed:
8093603
Citation
Wilson Savino, Claude Carnaud, Jian-Jian Luan, Jean-François Bach, Mireille Dardenne; Characterization of the Extracellular Matrix—Containing Giant Perivascular Spaces in the NOD Mouse Thymus. Diabetes 1 January 1993; 42 (1): 134–140. https://doi.org/10.2337/diab.42.1.134
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