Failure of CD25+ T cells from lupus-prone mice to suppress lupus glomerulonephritis and sialoadenitis.
The development of organ-specific autoimmune diseases in mice thymectomized on day 3 of life (d3tx mice) can be prevented by transferring CD4(+)CD25(+) T cells from syngeneic, normal adult mice. Using a d3tx model, we asked whether CD4(+)CD25(+) T cell deficiency contributes to glomerulonephritis (GN) in lupus-prone mice. New Zealand Mixed 2328 (NZM2328) mice spontaneously develop autoantibodies to dsDNA and female-dominant, fatal GN. After d3tx, both male and female NZM2328 mice developed 1) accelerated dsDNA autoantibody response, 2) early onset and severe proliferative GN with massive mesangial immune complexes, and 3) autoimmune disease of the thyroid, lacrimal gland, and salivary gland. The d3tx male mice also developed autoimmune prostatitis. The transfer of CD25(+) cells from 6-wk-old asymptomatic NZM2328 donors effectively suppressed dsDNA autoantibody and the development of autoimmune diseases, with the exception of proliferative lupus GN and sialoadenitis. This finding indicates that NZM2328 lupus mice have a selective deficiency in T cells that regulates the development of lupus GN and sialoadenitis. After d3tx, the proliferative GN of female mice progressed to fatal GN, but largely regressed in the male, thereby revealing a checkpoint in lupus GN progression that depends on gender.
Department of Pathology and University of Virginia Specialized Center of Research on Systemic Lupus Erythematosus, University of Virginia, Charlottesville, VA 22908, USA. hb5u@virginia.edu
Harini
H
Bagavant
Kenneth S K
KS
Tung
D000208:Acute Disease; D000367:Age Factors; D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis / Q000097:blood; D000936:Antigen-Antibody Complex / Q000097:blood / Q000378:metabolism; D002908:Chronic Disease; D004247:DNA / Q000276:immunology; D018450:Disease Progression; D005260:Female; D020022:Genetic Predisposition to Disease; D015432:Glomerulonephritis, Membranoproliferative / Q000276:immunology* / Q000503:physiopathology / Q000517:prevention & control; D007678:Kidney Glomerulus / Q000276:immunology / Q000378:metabolism; D007766:Lacrimal Apparatus Diseases / Q000517:prevention & control; D008181:Lupus Nephritis / Q000235:genetics* / Q000276:immunology* / Q000503:physiopathology; D008297:Male; D051379:Mice; D011472:Prostatitis / Q000517:prevention & control; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis*; D012737:Sex Factors; D012793:Sialadenitis / Q000276:immunology* / Q000503:physiopathology / Q000517:prevention & control; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D013934:Thymectomy; D013967:Thyroiditis, Autoimmune / Q000517:prevention & control
D000974:Antibodies, Antinuclear; D000936:Antigen-Antibody Complex; D015375:Receptors, Interleukin-2; D004247:DNA