title: Effect of Chronic Uremia on the Cell Surface Expression of B7 Family Costimulatory Molecules in an HLA-A2 Transgenic Mouse Model of Chronic Kidney Disease.
abstract: Uremia due to chronic kidney disease (CKD) in humans is associated with immune dysfunction, increased susceptibility to infections, immune-activation-associated inflammation, and poor responses to vaccines. The pathophysiologic basis of these immune defects is hypothesized to be associated with a wide range of immunologic abnormalities, including an inability to sufficiently express the B7 family (B7-1, CD80; B7-2, CD86) of T-cell costimulatory molecules. However, testing the hypothesis that a state of chronic uremia contributes to attenuated expression of CD80 or CD86 has been difficult because few animal models faithfully recapitulate the immune defects observed in human CKD patients. We used a humanized mouse in a model of surgically induced renal failure and secondary chronic uremia to evaluate the effect of uremia on the expression of these markers. In a manner that resembles the changes observed in CKD patients, surgically induced CKD in mice resulted in decreased costimulatory CD86 expression compared with that in sham-operated controls. Immunodeficiency was functionally demonstrated in this mouse model by documenting an attenuated immune response to a cholera-toxin-based hepatitis B vaccine. This model will be useful for investigating the mechanisms involved in chronic uremia-associated immunodeficiency, poor response to vaccination, and problems associated with immunization of CKD patients.
authors: Division of Allergy and Clinical Immunology, Department of Internal Medicine, Michigan Nanotechnology Institute for Medicine and Biological Sciences, University of Michigan, Ann Arbor, Michigan, USA. pmakidon@umich.edu.
authors: Paul E
authors: PE
authors: Makidon
authors: Division of Allergy and Clinical Immunology, Department of Internal Medicine, Michigan Nanotechnology Institute for Medicine and Biological Sciences, University of Michigan, Ann Arbor, Michigan, USA.
authors: Douglas M
authors: DM
authors: Smith
authors: Division of Allergy and Clinical Immunology, Department of Internal Medicine, Michigan Nanotechnology Institute for Medicine and Biological Sciences, University of Michigan, Ann Arbor, Michigan, USA.
authors: Jeffery V
authors: JV
authors: Groom Ii
authors: Division of Allergy and Clinical Immunology, Department of Internal Medicine, Michigan Nanotechnology Institute for Medicine and Biological Sciences, University of Michigan, Ann Arbor, Michigan, USA.
authors: Zhengyi
authors: Z
authors: Cao
authors: Division of Allergy and Clinical Immunology, Department of Internal Medicine, Michigan Nanotechnology Institute for Medicine and Biological Sciences, University of Michigan, Ann Arbor, Michigan, USA.
authors: Jeffery J
authors: JJ
authors: Landers
authors: Division of Allergy and Clinical Immunology, Department of Internal Medicine, Michigan Nanotechnology Institute for Medicine and Biological Sciences, University of Michigan, Ann Arbor, Michigan, USA.
authors: James R
authors: JR
authors: Baker
mesh_terms: D000818:Animals; D060887:B7 Antigens / Q000276:immunology* / Q000378:metabolism; D018122:B7-1 Antigen / Q000276:immunology / Q000378:metabolism; D051940:B7-2 Antigen / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005838:Genotype; D015789:HLA-A2 Antigen / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006510:Hepatitis B Antibodies / Q000097:blood; D017325:Hepatitis B Vaccines / Q000276:immunology; D006801:Humans; D007114:Immunization; D007074:Immunoglobulin G / Q000097:blood; D008822:Mice, Transgenic; D010641:Phenotype; D051436:Renal Insufficiency, Chronic / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D013154:Spleen / Q000276:immunology / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism; D015854:Up-Regulation; D014511:Uremia / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
chemical_list: D060887:B7 Antigens; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; D015789:HLA-A2 Antigen; D006510:Hepatitis B Antibodies; D017325:Hepatitis B Vaccines; D007074:Immunoglobulin G