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 alpha 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.


CONCLUSIONS
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.
Salama
Alan D
AD
Laboratory of Immunogenetics and Transplantation, Renal Division, Brigham and Women's Hospital and The Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA. asalama@hhnt.org
Chaudhry
Afzal N
AN
Holthaus
Kathryn A
KA
Mosley
Karen
K
Kalluri
Raghu
R
Sayegh
Mohamed H
MH
Lechler
Robert I
RI
Pusey
Charles D
CD
Lightstone
Liz
L
D000208:Acute Disease; D000328:Adult; D000368:Aged; D019867:Anti-Glomerular Basement Membrane Disease / Q000276:immunology*; D000906:Antibodies / Q000276:immunology; D001323:Autoantibodies; D001324:Autoantigens / Q000276:immunology*; D005260:Female; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology; D016753:Interleukin-10 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
D000906:Antibodies; D001323:Autoantibodies; D001324:Autoantigens; D015375:Receptors, Interleukin-2; C051951:antiglomerular basement membrane antibody; D016753:Interleukin-10