T-CELL SUBSET MODULATION OF IMMUNOGLOBULIN PRODUCTION IN IGA NEPHROPATHY AND MEMBRANOUS GLOMERULONEPHRITIS

Monoclonal antibodies directed against T cell subset antigens were used to deplete peripheral blood human mononuclear cells from helper (OKT4+) and suppressor/cytotoxic (OKT8+) cells. Unfractionated cells and depleted cells were assayed for their capacity to modulate pokeweed mitogen (PWM)-driven IgG, IgA, and IgM production by autologous B lymphocytes. Ig production in the presence of these various cell preparations paralleled the OKT4+/OKT8+ ratio defining the population. There was no clear relationship between the level of PWM-driven Ig production by unfractionated cells and their initial relative content in OKT4+ and OKT8+ cells. Patients with IgA nephropathy and membranous glomerulonephritis showed a statistically significant increase of OKT4+/OKT8+ ratio, suggestive of suppressor T cell deficiency. There was no increase in IgA production in patients with IgA nephropathy, even in those showing high serum IgA level. A special feature found in patients with IgA nephropathy, irrespective of OKT4+/OKT8+ ratio in unfractionated cells, was a particularly intense enhancement of IgA production after OKT8+ cell depletion in some of the patients, contrasting with a particularly low effect of such depletion on the synthesis of all Ig classes in other patients. In patients with membranous glomerulonephritis there was no obvious abnormality in the modulation of Ig production by T cell subsets, with the exception of a weak suppressor activity with respect only to IgM production in a significant number of patients.