title: Naturally occurring IgM anti-leukocyte autoantibodies (IgM-ALA) inhibit T cell activation and chemotaxis.
abstract: The physiological relevance of naturally occurring IgM-ALA remains to be elucidated. These autoantibodies are present from birth and increase in diverse inflammatory states that are both infectious and noninfectious. Clinical observations showing significantly less acute allograft rejections in recipients having high IgM-ALA levels, led us to investigate whether IgM-ALA could have a functional role in attenuating T cell mediated inflammatory responses. In pursuit of this hypothesis, we did studies using IgM purified from the serum of normal individuals, patients with end stage renal disease, and HIV-1 infection. All preparations of IgM immunoprecipitated certain receptors e.g., CD3, CD4, CCR5, and CXCR4 from whole cell lysates but failed to immunoprecipitate IL-2R and HLA Ags. In physiological doses IgM down-regulated CD4, CD2 and CD86 but not CD8 and CD28, inhibited T cell proliferation, decreased production of certain proinflammatory cytokines e.g., TNF-alpha, IL-13 and IL-2, but not IFN- gamma, IL-1beta, GM-CSF, IL-6 and IL-8 and inhibited leukocyte chemotaxis. These inhibitory effects were more pronounced when using IgM from patients with high levels of IgM-ALA and these inhibitory effects were significantly reduced after using IgM preabsorbed with leukocytes. IgM-ALA binding to leukocytes was found to be highly specific, as <10% of IgM secreting B cell clones had IgM-ALA specificity with some clones having specificity for either T cells or monocytes. These findings support the concept that IgM-ALA provides an innate mechanism to regulate T cell mediated inflammatory responses.
authors.affiliation: Division of Nephrology, Department of Internal Medicine and Nephrology, University of Virginia Health System, Charlottesville, VA 22908, USA. pil@virginia.edu
authors.forename: Peter I
authors.initials: PI
authors.lastname: Lobo
authors.forename: Kailo H
authors.initials: KH
authors.lastname: Schlegel
authors.forename: Clinton E
authors.initials: CE
authors.lastname: Spencer
authors.forename: Mark D
authors.initials: MD
authors.lastname: Okusa
authors.forename: Christopher
authors.initials: C
authors.lastname: Chisholm
authors.forename: Nino
authors.initials: N
authors.lastname: McHedlishvili
authors.forename: Andrew
authors.initials: A
authors.lastname: Park
authors.forename: Constance
authors.initials: C
authors.lastname: Christ
authors.forename: Christopher
authors.initials: C
authors.lastname: Burtner
mesh_terms: D001323:Autoantibodies / Q000302:isolation & purification / Q000494:pharmacology*; D001402:B-Lymphocytes / Q000187:drug effects; D017252:CD3 Complex / Q000276:immunology; D015704:CD4 Antigens / Q000187:drug effects / Q000378:metabolism; D002464:Cell Migration Inhibition; D002478:Cells, Cultured; D002633:Chemotaxis / Q000187:drug effects*; D016207:Cytokines / Q000037:antagonists & inhibitors; D015536:Down-Regulation; D006801:Humans; D007075:Immunoglobulin M / Q000302:isolation & purification / Q000494:pharmacology*; D047468:Immunoprecipitation; D008213:Lymphocyte Activation / Q000187:drug effects*; D019713:Receptors, CCR5 / Q000276:immunology; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D014470:Umbilical Cord / Q000276:immunology; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000037:antagonists & inhibitors
chemical_list: D001323:Autoantibodies; D017252:CD3 Complex; D015704:CD4 Antigens; D016207:Cytokines; D007075:Immunoglobulin M; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D051746:ZAP-70 Protein-Tyrosine Kinase