Th1 polarization in murine IgA nephropathy directed by bone marrow-derived cells.
IgA nephropathy is the most common form of progressive glomerulonephritis although the pathophysiology of this nephropathy is unclear. The ddY mouse is a spontaneous animal model with variable incidence and extent of glomerular injury mimicking human IgA nephropathy. Here, we transplanted bone marrow cells from 20-week-old ddY mice with beginning or quiescent IgA nephropathy into irradiated similar ddY mice, C57Bl/6 (Th1 prone) mice, or BALB/c (Th2 prone) mice. Serum IgA/IgG complex and Th1/Th2 polarization of spleen cells was determined by enzyme-linked immunosorbent assay and confirmed by fluorescent cytometric analysis. The ddY mice with commencing IgA nephropathy demonstrated strong polarization toward Th1, while those with quiescent disease were Th2 polarized. Serum levels of IgA/IgG2a immune complex significantly correlated with the severity of the glomerular lesions. Bone marrow taken from mice with commencing IgA nephropathy conferred IgA nephropathy with Th1 polarization in recipient-quiescent mice, while transplantation from the quiescent mice ablated glomerular injury and mesangial IgA/IgG deposition in those commencing IgA disease. However, adoptive transfer of CD4(+) T cells from those whose disease began failed to induce any IgA deposition or renal injury. Our study suggests that bone marrow cells, presuming IgA producing cells, may initiate this disease. Th1 cells may be involved in the pathophysiology of the disease after glomerular IgA deposition.
Suzuki
H
H
Division of Nephrology, Department of Internal Medicine, Juntendo University School of Medicine, Tokyo, Japan.
Suzuki
Y
Y
Aizawa
M
M
Yamanaka
T
T
Kihara
M
M
Pang
H
H
Horikoshi
S
S
Tomino
Y
Y
D019264:Adoptive Transfer / Q000379:methods; D000818:Animals; D000936:Antigen-Antibody Complex / Q000378:metabolism; D001854:Bone Marrow Cells / Q000473:pathology / Q000502:physiology*; D016026:Bone Marrow Transplantation; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology / Q000502:physiology; D004195:Disease Models, Animal; D005260:Female; D005922:Glomerulonephritis, IGA / Q000473:pathology* / Q000503:physiopathology*; D007070:Immunoglobulin A / Q000378:metabolism; D007074:Immunoglobulin G / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D013154:Spleen / Q000166:cytology; D018417:Th1 Cells / Q000276:immunology / Q000473:pathology / Q000502:physiology*; D018418:Th2 Cells / Q000276:immunology / Q000473:pathology / Q000502:physiology
D000936:Antigen-Antibody Complex; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D015847:Interleukin-4; D007371:Interferon-gamma