Low-density cells isolated from the rat thymus resemble branched cortical macrophages and have a reduced capability of rescuing double-positive thymocytes from apoptosis in the BB-DP rat

• Published in: Journal of leukocyte biology Vol. 82; no. 4; pp. 869 - 876
• Main Authors: Sommandas, Vinod, Rutledge, Elizabeth A., Van Yserloo, Brian, Fuller, Jessica, Lernmark, Åke, Drexhage, Hemmo A.
• Format: Journal Article
• Language: English
• Published: United States Society for Leukocyte Biology 01.10.2007
• Subjects: ADP Ribose Transferases - deficiency; ADP Ribose Transferases - immunology; Animals; Antigen-Presenting Cells - cytology; Antigen-Presenting Cells - immunology; Antigens, Differentiation - genetics; Antigens, Differentiation - immunology; Apoptosis - genetics; Apoptosis - immunology; autoimmunity; Autoimmunity - genetics; Cell Separation; Cell Shape - genetics; Cell Shape - immunology; Clinical Medicine; Endocrinology and Diabetes; Endokrinologi och diabetes; Epithelial Cells - cytology; Epithelial Cells - immunology; Flow Cytometry; Immune Tolerance - genetics; Immune Tolerance - immunology; Intracellular Signaling Peptides and Proteins - deficiency; Intracellular Signaling Peptides and Proteins - immunology; Klinisk medicin; Lymphopenia - genetics; Lymphopenia - immunology; Macrophages - cytology; Macrophages - immunology; Medical and Health Sciences; Medicin och hälsovetenskap; Organ Specificity - genetics; Organ Specificity - immunology; positive selection; Rats; Rats, Inbred F344; Rats, Mutant Strains; Rats, Wistar; Species Specificity; T-Lymphocytes, Regulatory - cytology; T-Lymphocytes, Regulatory - immunology; Thymus Gland - cytology; Thymus Gland - immunology; type I diabetes
• ISSN: 0741-5400; 1938-3673
• DOI: 10.1189/jlb.0407213

Biobreeding‐diabetes prone (BB‐DP) rats spontaneously develop organ‐specific autoimmunity and are severely lymphopenic and particularly deficient in ART2+ regulatory T cells. A special breed, the so‐called BB‐diabetic‐resistant (DR) rats, are not lymphopenic and do not develop organ‐specific autoimmunity. The genetic difference between both strains is the lymphopenia (lyp) gene. Intrathymic tolerance mechanisms are important to prevent autoimmunity, and next to thymus epithelial cells, thymus APC play a prominent part in this tolerance. We here embarked on a study to detect defects in thymus APC of the BB‐DP rat and isolated thymus APC using a protocol based on the low‐density and nonadherent character of the cells. We used BB‐DP, BB‐DR, wild‐type F344, and F344 rats congenic for the lyp gene‐containing region. The isolated thymus, nonadherent, low‐density cells appeared to be predominantly ED2+ branched cortical macrophages and not OX62+ thymus medullary and cortico‐medullary dendritic cells. Functionally, these ED2+ macrophages were excellent stimulators of T cell proliferation, but it is more important that they rescued double‐positive thymocytes from apoptosis. The isolated thymus ED2+ macrophages of the BB‐DP and the F344.lyp/lyp rat exhibited a reduced T cell stimulatory capacity as compared with such cells of nonlymphopenic rats. They had a strongly diminished capability of rescuing thymocytes from apoptosis (also of ART2+ T cells) and showed a reduced Ian5 expression (as lyp/lyp thymocytes do). Our experiments strongly suggest that branched cortical macrophages play a role in positive selection of T cells in the thymus and point to defects in these cells in BB‐DP rats.