Decreased CD4+CD25+ cells and increased dimeric IgA-producing cells in tonsils in IgA nephropathy.
BACKGROUND
The relationship between tonsillar autoimmune response and the pathogenesis of IgA nephropathy (IgAN) has been previously demonstrated. However, the role of CD4+CD25+ cells, which play critical roles in maintaining peripheral tolerance and preventing autoimmunity, has not yet been defined in IgAN.


METHODS
The lymphocytes from tonsils of all subjects (including 37 IgAN cases and 37 controls without renal diseases) were cultured for 72 hours without stimulation, or with stimulation by alpha-hemolytic streptococcus (HS) isolated from the tonsillar crypts of cases (the HS-IgAN) or controls (HS-controls). The CD4+CD25+ cells were measured by flow cytometry. Expression of J chain mRNA was analyzed by in situ hybridization (ISH) and the dimeric IgA-producing cells were identified by immunofluorescence and fluorescent ISH.


RESULTS
The number of CD4+CD25+ cells was significantly lower in cases than in controls (0.98% +/- 0.204% vs. 3.58% +/- 0.554%, 1.37% +/- 0.214% vs. 5.78% +/- 0.562%, and 1.43% +/- 0.202% vs. 6.05% +/- 0.521%, for nonstimulation, HS-controls and HS-cases, respectively). CD4+CD25+ cells from cases showed a significantly lower stimulation index (SI) when stimulated with HS-controls and HS-IgAN than controls (p<0.05), whereas the number of dimeric IgA-producing cells was significantly higher in cases than controls (11.9% +/- 3.1% vs. 6.5% +/- 1.5%, 33.5% +/- 5.7% vs. 13.9% +/- 1.2%, and 35.1% +/- 6.2% vs. 13.9% +/- 1.2%, for nonstimulation, HS-controls and HS-cases, respectively). The dimeric IgA-producing cells from patients with IgAN showed a significantly higher SI when stimulated with HS-controls, or HS-IgAN than those from patients without renal disease (p<0.01). The SI of CD4+CD25+ cells was negatively correlated with that of dimeric IgA-producing cells.


CONCLUSIONS
The results suggest that CD4+CD25+ cells and dimeric IgA-producing cells in tonsils may be related to the pathogenesis of IgAN.
Huang
Hongdong
H
Hunan Key Laboratory of Nephrology and Hemoperfusion, Division of Nephrology, Second Xiangya Hospital of Central South University, Changsha, Hunan Province - PR China.
Peng
Youming
Y
Liu
Hong
H
Yang
Xinming
X
Liu
Fuyou
F
D000293:Adolescent; D000328:Adult; D000921:Antibody-Producing Cells / Q000276:immunology* / Q000382:microbiology; D015551:Autoimmunity; D016022:Case-Control Studies; D002478:Cells, Cultured; D002648:Child; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D005922:Glomerulonephritis, IGA / Q000150:complications / Q000276:immunology*; D006801:Humans; D007070:Immunoglobulin A / Q000235:genetics / Q000378:metabolism*; D007144:Immunoglobulin J-Chains / Q000378:metabolism; D017404:In Situ Hybridization, Fluorescence; D053645:Interleukin-2 Receptor alpha Subunit / Q000032:analysis*; D008297:Male; D014066:Palatine Tonsil / Q000276:immunology* / Q000382:microbiology; D055503:Protein Multimerization; D012333:RNA, Messenger / Q000378:metabolism; D013291:Streptococcus / Q000302:isolation & purification; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000382:microbiology; D014068:Tonsillectomy; D014069:Tonsillitis / Q000276:immunology* / Q000382:microbiology / Q000601:surgery; D055815:Young Adult
C508017:IL2RA protein, human; D007070:Immunoglobulin A; D007144:Immunoglobulin J-Chains; D053645:Interleukin-2 Receptor alpha Subunit; D012333:RNA, Messenger