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Summary The aetiology of IgA nephropathy (IgAN) is closely related with abnormality of mucosal immunity. We investigated the roles of gamma delta T cells in the regulation of IgA production by B cells in IgAN patients. The proportion of gamma delta T cells in peripheral blood mononuclear cells (PBMNC) was higher in IgAN patients than in the controls and was found to be correlated with the proportion of surface IgA-positive (sIgA+) B cells, which are precursors of IgA-secreting plasma cells. After in vitro PWM stimulation, sIgA expression on B cells and IgA production were significantly enhanced in PBMNC obtained from IgAN patients, whereas the enhancements were abolished by removal of gamma delta T cells from the PBMNC. Purified gamma delta T cells from IgAN patients induced surface IgA expression on naive sIgD+ B cells more effectively than did alpha beta T cells. Moreover, stimulated gamma delta T cells from IgAN patients produced a larger amount of TGF-beta 1, which is one of the main cytokines that induces IgA class switching on B cells, as compared with alpha beta T cells and control gamma delta T cells. The expanded gamma delta T cells from IgAN patients exclusively expressed V gamma 9, and the nucleotide sequences of junctional regions of V gamma 9 showed very limited TCR diversities. It was therefore concluded that gamma delta T cells, which are expanded in response to specific antigens, enhance IgA class switching on B cells in IgAN patients. [ABSTRACT FROM AUTHOR]