title: Naturally occurring IgM anti-leukocyte autoantibodies inhibit T-cell activation and chemotaxis.
abstract: BACKGROUND
  Naturally occurring IgM antileukocyte autoantibodies (IgM-ALA) are present from birth and increase during inflammatory processes of diverse etiologies. The clinical observation demonstrating a significant correlation (P < 01) between lack of acute rejections and presence of high levels of IgM-ALA in recipients of kidney allografts prompted us to study if IgM-ALA alters T-cell function and leukocyte chemotaxis.
  
  
  METHODS
  In-vitro functional assays were performed using leucocytes isolated from human peripheral blood. In-vivo studies were performed in C57BL6 mice.
  
  
  RESULTS
  Human studies revealed that IgM-ALA consist of several different IgM, each with specificities for a different leukocyte receptor, e.g., CD3, CD4, CCR5, and CXCR4. We show that IgM inhibits T-cell activation, proliferation, and chemotaxis. Data on in vivo murine models of ischemia-reperfusion injury and cardiac transplantation support our hypothesis.
  
  
  CONCLUSIONS
  The innate anti-inflammatory mechanism of IgM-ALA can be exploited by using purified normal IgM to inhibit inflammatory states or by a vaccine approach to increase in vivo production of IgM-ALA (e.g., prior to a transplant).
authors.affiliation: Center for Immunity, Inflammation and Regenerative Medicine, University of Virginia, 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: Schlegal
authors.forename: John
authors.initials: J
authors.lastname: Vengal
authors.forename: Mark D
authors.initials: MD
authors.lastname: Okusa
authors.forename: Hong
authors.initials: H
authors.lastname: Pei
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000276:immunology / Q000494:pharmacology*; D016175:B-Lymphocyte Subsets / Q000276:immunology; D002455:Cell Division / Q000187:drug effects; D002464:Cell Migration Inhibition / Q000187:drug effects*; D005312:Fetal Blood / Q000166:cytology; D015483:HIV Antibodies / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology*; D007231:Infant, Newborn; D007676:Kidney Failure, Chronic / Q000276:immunology; D016030:Kidney Transplantation / Q000276:immunology; D007962:Leukocytes / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects*; D008222:Lymphokines / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D010766:Phosphorylation / Q000187:drug effects; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D011971:Receptors, Immunologic / Q000187:drug effects / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000378:metabolism
chemical_list: D001323:Autoantibodies; D015483:HIV Antibodies; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D008222:Lymphokines; D011971:Receptors, Immunologic; D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human
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