Journal
CLINICAL AND EXPERIMENTAL IMMUNOLOGY
Volume 124, Issue 1, Pages 110-117Publisher
BLACKWELL PUBLISHING LTD
DOI: 10.1046/j.1365-2249.2001.01494.x
Keywords
gamma delta T cells; IgA nephropathy; IgA switching; TGF-beta
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The aetiology of IgA nephropathy (IgAN) is closely related with abnormality of mucosal immunity. We investigated the roles of gammadelta T cells in the regulation of IgA production by B cells in IgAN patients. The proportion of gammadelta 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 gammadelta T cells from the PBMNC. Purified gammadelta T cells from IgAN patients induced surface IgA expression on naive sIgD+ B cells more effectively than did alphabeta T cells. Moreover, stimulated gammadelta T cells from IgAN patients produced a larger amount of TGF-beta1, which is one of the main cytokines that induces IgA class switching on B cells, as compared with alphabeta T cells and control gammadelta T cells. The expanded gammadelta T cells from IgAN patients exclusively expressed Vgamma9, and the nucleotide sequences of junctional regions of Vgamma9 showed very limited TCR diversities. It was therefore concluded that gammadelta T cells, which are expanded in response to specific antigens, enhance IgA class switching on B cells in IgAN patients.
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