T-CELL AND B-CELL RESPONSES FOLLOWING IMMUNIZATION WITH TETANUS TOXOID IN IGA NEPHROPATHY

The B and T cell responses were investigated in IgA nephropathy before and after immunization with tetanus toxoid (TT). Both IgA and IgG ant i-tetanus toxoid antibodies were elicited, but the IgA antibodies were significantly greater in patients (92.6 +/- 11.7 ELISA units) than in the controls (49.2 +/- 7.5 ELISA units). This was associated with a s ignificantly greater proportion of IgA + B cells in patients than cont rols before immunization. However, a significant increase in the propo rtion of IgA1 binding CD4 and CD8 cells was also found. The proportion of CD3 cells with gamma-delta-T cell receptors (CD3+ TCR-gamma-delta), was significantly greater before immunization in the IgA nephropath y patients (37.0% +/- 2.4), compared with controls (10.0% +/- 2.3; P < 0.001). Immunization with TT further enhanced the CD3+ TCR-gamma-delt a+ cells in patients to 45.8% +/- 7.2 compared with controls (16.3% +/ - 4.5), with a corresponding decrease in CD3+ TCR-alpha-beta+ cells in the patients (P < 0.001). CD3+ TCR-gamma-delta+ cells are upregulated by common microbial antigens and clinical exacerbations of IgA nephro pathy are frequently associated with mucosal infections and a rise in serum IgA concentration. The increased TCR-gamma-delta expression may be responsible for the enhanced IgA antibody response in IgA nephropat hy. The increase in IgA antibodies may then exert a controlling effect by binding to augmenting T cells and thereby inhibiting their functio n.