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* Department of Internal Medicine and Nephrology,
Charles O. Strickler Transplant Center,
Department of Obstetrics and Gynecology,
Center for Immunity, Inflammation, and Regenerative Medicine, and
¶ Bernie-Carter Immunology Center, University of Virginia, Charlottesville, VA 22908
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-
, IL-13 and IL-2, but not IFN- 
, IL-1β, 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.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by National Institutes of Health, National Institute of Allergy and Infectious Disease Grant 5R21AI052740-02 (to P.I.L.), funds from the Nephrology Division Research Development Funds, University of Virginia Research Development funds, and the Fillipo Research Funds.
2 Address correspondence and reprint requests to Dr. Peter I. Lobo, Department of Internal Medicine and Nephrology, University of Virginia Health System, P.O. Box 800133 Charlottesville, VA 22908. E-mail address: pil{at}virginia.edu
3 Abbreviations used in this paper: IgM-ALA, IgM anti-leukocyte autoantibodies; ESRD, end-stage renal disease patients; MCF, mean (geometric) channel fluorescence.
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  J.-J. Liao, M.-C. Huang, K. Fast, K. Gundling, M. Yadav, J. R. Van Brocklyn, M. R. Wabl, and E. J. Goetzl Immunosuppressive human anti-lymphocyte autoantibodies specific for the type 1 sphingosine 1-phosphate receptor FASEB J, June 1, 2009; 23(6): 1786 - 1796. [Abstract] [Full Text] [PDF]
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