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

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Abstract
Autoantibodies 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.