title: The development of autoimmune features in aging mice is closely associated with alterations of the peripheral CD4⁺ T-cell compartment.
abstract: Some signs of potential autoimmunity, such as the appearance of antinuclear antibodies (ANAs) become prevalent with age. In most cases, elderly people with ANAs remain healthy. Here, we investigated whether the same holds true for inbred strains of mice. Indeed, we show that most mice of the C57BL/6 (B6) strain spontaneously produced IgG ANA at 8-12 months of age, showed IgM deposition in kidneys and lymphocyte infiltrates in submandibular salivary glands. Despite all of this, the mice remained healthy. ANA production is likely CD4(+) T-cell dependent, since old (40-50 weeks of age) B6 mice deficient for MHC class II do not produce IgG ANAs. BM chimeras showed that ANA production was not determined by age-related changes in radiosensitive, hematopoietic progenitor cells, and that the CD4(+) T cells that promote ANA production were radioresistant. Thymectomy of B6 mice at 5 weeks of age led to premature alterations in T-cell homeostasis and ANA production, by 15 weeks of age, similar to that in old mice. Our findings suggest that a disturbed T-cell homeostasis may drive the onset of some autoimmune features.
authors.affiliation: Developmental and Molecular Immunology, Department of Biomedicine, University of Basel, Basel, Switzerland.
authors.forename: Anja
authors.initials: A
authors.lastname: Nusser
authors.forename: Natko
authors.initials: N
authors.lastname: Nuber
authors.forename: Oliver F
authors.initials: OF
authors.lastname: Wirz
authors.forename: Hannie
authors.initials: H
authors.lastname: Rolink
authors.forename: Jan
authors.initials: J
authors.lastname: Andersson
authors.forename: Antonius
authors.initials: A
authors.lastname: Rolink
mesh_terms: D000375:Aging / Q000276:immunology*; D000818:Animals; D000974:Antibodies, Antinuclear / Q000097:blood / Q000276:immunology; D015551:Autoimmunity / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D019084:Fluorescent Antibody Technique, Indirect; D006706:Homeostasis / Q000276:immunology*; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D000974:Antibodies, Antinuclear
keywords: Antinuclear antibody; Autoimmunity; Sjögren's syndrome; T-cell homeostasis