An increased frequency of autoantibody-inducing CD4+ T cells in pre-diseased lupus-prone mice.
Pathogenic autoantibody production in murine models of lupus is dependent on autoreactive CD4+ helper T cells. However, the mechanisms which permit the selection and maintenance of this autoantibody-inducing CD4+ T-cell repertoire are currently unknown. We hypothesized that the peripheral CD4+ T-cell repertoire of lupus-prone mice was enriched with autoantibody-inducing specificities. To test this, we utilized the splenic focus assay to determine if pre-diseased lupus-prone (NZB x NZW)F(1) mice have an elevated frequency of autoreactive CD4+ T lymphocytes capable of supporting autoantibody production. The splenic focus limiting dilution assay permits anti-nuclear antibodies to be generated from contact-dependent T-B interactions in vitro. We show that young, pre-diseased lupus-prone mice have an elevated frequency of autoantibody-inducing CD4+ T cells. Interestingly, these autoantibody-inducing CD4+ T-cell responses are also present in the thymus. Therefore, an elevated frequency of autoantibody-inducing CD4+ T cells predisposes lupus-prone mice to the development of autoantibodies.
Busser
Brian W
BW
Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Cancro
Michael P
MP
Laufer
Terri M
TM
D000818:Animals; D000974:Antibodies, Antinuclear / Q000276:immunology*; D000917:Antibody Formation / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002450:Cell Communication / Q000276:immunology*; D002478:Cells, Cultured; D008177:Lupus Vulgaris / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008814:Mice, Inbred NZB; D013154:Spleen / Q000276:immunology* / Q000473:pathology; D013950:Thymus Gland / Q000276:immunology* / Q000473:pathology
D000974:Antibodies, Antinuclear