Cell Biology – Immunology – Pathology
Kidney International (2003) 64, 1685–1694; doi:10.1046/j.1523-1755.2003.00259.x
Regulation by CD25+ lymphocytes of autoantigen-specific T-cell responses in Goodpasture's (anti-GBM) disease
Alan D Salama, Afzal N Chaudhry, Kathryn A Holthaus, Karen Mosley, Raghu Kalluri, Mohamed H Sayegh, Robert I Lechler, Charles D Pusey and Liz Lightstone
Laboratory of Immunogenetics and Transplantation, Renal Division, Brigham and Women's Hospital and The Children's Hospital, Harvard Medical School, Boston, Massachusetts; Program in Matrix Biology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts; and Renal Section and Department of Immunology, Division of Medicine, Imperial College London, Hammersmith Hospital, London, United Kingdom
Correspondence: Dr Alan D. Salama, Laboratory of Immunogenetics and Transplantation, Brigham and Women's Hospital, 75 Francis Street, Boston, MA, 02115. E-mail: asalama@hhnt.org
Received 25 January 2003; Revised 29 May 2003; Accepted 17 June 2003.
Abstract
Regulation by CD25+ lymphocytes of autoantigen-specific T-cell responses in Goodpasture's (anti-GBM) disease.
Background
Goodpasture's, or anti-glomerular basement membrane (GBM), disease is unusual among autoimmune diseases in that it rarely follows a relapsing-remitting course. Moreover, untreated, autoantibodies disappear spontaneously after 1 to 3 years and, following treatment, autoreactive T cells diminish in frequency. This suggests that operational tolerance toward the autoantigen is reestablished. However, the mechanisms underlying this have remained unclear. Recent data have suggested that a population of regulatory T lymphocytes can suppress both autoimmune and alloimmune responses in animal models and are present in normal individuals. However, to date, they have not been demonstrated to play a role in human renal autoimmune disease.
Methods
We studied the role of regulatory CD25+ cells in suppressing T-cell responses to the Goodpasture autoantigen in nine patients with Goodpasture's disease.
Results
At the time of acute presentation, there was no evidence of a regulatory cell population. However, from 3 months onward a population emerged, capable of suppressing the response to the Goodpasture autoantigen. Following depletion of CD25+ cells, the frequencies of autoreactive-, GBM-, or collagen 
3(IV)NC1-specific T cells were significantly increased (P = 0.031 by paired t test), with five of seven (71%) convalescent patients and no acute patients demonstrating regulation.
Conclusion
These data demonstrate that, in Goodpasture's disease, regulatory CD25+ T cells play a role in inhibiting the autoimmune response. Their emergence and persistence may underlie the "single hit" nature of this condition. Understanding the conditions required for the development and propagation of these cells would allow development of novel therapeutic strategies for inducing hyporesponsiveness in autoimmune disease.
Keywords:
tolerance, glomerulonephritis, anti-GBM disease, T cells, regulatory cells
