6533b832fe1ef96bd129add2

RESEARCH PRODUCT

Liver-infiltrating T helper cells in autoimmune chronic active hepatitis stimulate the production of autoantibodies against the human asialoglycoprotein receptor in vitro.

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SUMMARYAutoantibodies against the human asialoglycoprotein receptor (ASGPR) occur in the sera orpaticnts with autoimmune liver disorders. Live-nfiltrating T cell clones that specifically recognize the ASGPR have been described in patients with autoimmune chronic active hepatitis (A-AH) and primary biliary cirrhosis (PBC). Recently, we have shown that peripheral blood mononuclcar cells (PBMC) from patients with A-AH or PBC but not chronic viral hepatitis secreted ant-SGPR antibodies in vitro. In this study we characterized the influence of live-nfiltrating T cells on the secretion of ASGP-pecific autoantibodies by autologous B cells in cell culture supernatants. T cell clones from liver biopsies of three patients with chronic autoimmune liver disorders (one with A-AH, two with PBC) were isolated and investigated for their proliferative response to soluble ASGPR and their helper function provided to autoantibod-ecrcting B lymphocytes. PBMC from these patients secreted autoantibodies spontaneously in their cell culture supematants and showed a proliferative response to ASGPR. T cel-epleted PBMC, however, lacked spontaneous antibody secretion. Four CD4+ CD8− live-nfiltrating T cell clones showed a proliferative response to ASGPR and also induced spontaneous ant-SGPR antibody production in cell culture supernatants when added to autologous T cell depleted PBMC. Activated supernatants of these T cell clones failed to induce antibody production. None of seven CD4+CD8− and two CD4−CD8+ T cell clones no-esponding to ASGPR provided this help for antibody secretion. Ant-SGPR secretion in vitro could not be inhibited by the addition of MoAbs raised against monomorphic determinants on HLA class II molecules. The addition of purified ASGPR or polyclona-ctivating pokeweed mitogen showed no influence on the production of autoantibodies in these cultures. These data show that B lymphocytes require T cell help for the production of ASGP-pecific antibodies. This help can be provided by ASGP-esponsive T helper cells via cellular interactions.