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International Immunology Advance Access published online on May 24, 2004
International Immunology, doi:10.1093/intimm/dxh101
© 2004 by The Japanese Society for Immunology
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Received February 23, 2004
Accepted April 21, 2004

Article

An increased frequency of autoantibody-inducing CD4+ T cells in pre-diseased lupus-prone mice

Brian W. Busser 1, Michael P. Cancro 2, Terri M. Laufer 1*

1 Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
2 Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA

* To whom correspondence should be addressed. E-mail: tlaufer{at}mail.med.upenn.edu.


  Abstract

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)F1 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.

Keywords: autoantibodies, B lymphocytes, lupus, T lymphocytes


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