T cell cytokine polarity as a determinant of immunoglobulin A (IgA) glycosylation and the severity of experimental IgA nephropathy.
Immunoglobulin A (IgA) glycosylation, recognized as an important pathogenic factor in IgA nephropathy (IgAN), is apparently controlled by the polarity of T helper (Th) cytokine responses. To examine the role of cytokine polarity in IgAN, inbred mice were immunized by intraperitoneal priming with inactivated Sendai virus (SeV) emulsified in either complete Freund's adjuvant (CFA) or incomplete Freund's adjuvant (IFA), which promote Th1- or Th2-immune response, respectively, and then boosted identically twice orally with aqueous suspensions of inactivated virus. Next, some mice were challenged intranasally with infectious SeV. Mice primed with CFA or IFA had equal reductions in nasal viral titre relative to non-immune controls, and equally increased serum levels of SeV-specific IgA antibody. Mice primed with CFA showed higher SeV-specific IgG than those with IFA. Splenocytes from mice primed with IFA produced copious amounts of interleukin (IL)-4 and IL-5, but little interferon-gamma and IL-2; those primed with CFA had reciprocal cytokine recall responses. Total serum IgA and especially SeV-specific IgA from mice primed with IFA showed a selective defect in sialylation and galactosylation. Although the frequency and intensity of glomerular deposits and haematuria did not differ, glomerulonephritis in mice primed with IFA and challenged with infectious virus was more severe than in those given CFA, as judged by serum creatinine level. We conclude that the polarity of T cell cytokines controls the pattern of IgA glycosylation and exerts direct or indirect effects on functional glomerular responses to immune complex deposition.
Chintalacharuvu
S R
SR
Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA.
Yamashita
M
M
Bagheri
N
N
Blanchard
T G
TG
Nedrud
J G
JG
Lamm
M E
ME
Tomino
Y
Y
Emancipator
S N
SN
D000276:Adjuvants, Immunologic; D000818:Animals; D016207:Cytokines / Q000276:immunology* / Q000378:metabolism; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005620:Freund's Adjuvant; D005922:Glomerulonephritis, IGA / Q000276:immunology*; D006031:Glycosylation; D007070:Immunoglobulin A / Q000097:blood / Q000276:immunology*; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D008055:Lipids; D051379:Mice; D008807:Mice, Inbred BALB C; D017817:Nasal Lavage Fluid / Q000276:immunology; D029082:Sendai virus / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism
D000276:Adjuvants, Immunologic; D016207:Cytokines; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D008055:Lipids; C114843:incomplete Freund's adjuvant; D005620:Freund's Adjuvant