title: 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.
abstract: 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.
authors.affiliation: Department of Immunology, Erasmus MC, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands. v.sommandas@erasmusmc.nl
authors.forename: Vinod
authors.initials: V
authors.lastname: Sommandas
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Rutledge
authors.forename: Brian
authors.initials: B
authors.lastname: Van Yserloo
authors.forename: Jessica
authors.initials: J
authors.lastname: Fuller
authors.forename: Ake
authors.initials: A
authors.lastname: Lernmark
authors.forename: Hemmo A
authors.initials: HA
authors.lastname: Drexhage
mesh_terms: D036002:ADP Ribose Transferases / Q000172:deficiency / Q000276:immunology; D000818:Animals; D000938:Antigen-Presenting Cells / Q000166:cytology* / Q000276:immunology; D000943:Antigens, Differentiation / Q000235:genetics / Q000276:immunology; D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D015551:Autoimmunity / Q000235:genetics; D002469:Cell Separation; D048430:Cell Shape / Q000235:genetics / Q000276:immunology; D004847:Epithelial Cells / Q000166:cytology / Q000276:immunology; D005434:Flow Cytometry; D007108:Immune Tolerance / Q000235:genetics / Q000276:immunology; D047908:Intracellular Signaling Peptides and Proteins / Q000172:deficiency / Q000276:immunology; D008231:Lymphopenia / Q000235:genetics / Q000276:immunology; D008264:Macrophages / Q000166:cytology* / Q000276:immunology; D009928:Organ Specificity / Q000235:genetics / Q000276:immunology; D051381:Rats; D011916:Rats, Inbred F344; D011922:Rats, Mutant Strains; D017208:Rats, Wistar; D013045:Species Specificity; D050378:T-Lymphocytes, Regulatory / Q000166:cytology* / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology* / Q000276:immunology
chemical_list: D000943:Antigens, Differentiation; D047908:Intracellular Signaling Peptides and Proteins; C459465:OX-62 antigen, rat; D036002:ADP Ribose Transferases