DEFECTIVE PROLIFERATION AND REGULATORY FUNCTION OF CD4+ T-CELLS BEARING LEU-8 HOMING RECEPTOR IN PRIMARY BILIARY-CIRRHOSIS

The majority of circulating CD4(+) T cells express the Leu-peripheral lymph node homing receptor, and these cells have previously been shown to have suppressor-inducer and suppressor function. In the present study, it was found that CD4(+) Leu-8(+) T cells from patients with primary biliary cirrhosis (PBC) have a significantly (P < 0.01) lower proliferative response when stimulated with phytohemagglutinin (PHA), concanavalin A (Con A), or pokeweed mitogen (PWM) compared to normal controls. The proliferative response of CD4(+), Leu-8(-) T cells was similar in patients and controls. However; the proliferative responses of CD4(+) Leu-8(+) from patients with PBC was normal when cells were stimulated with PHA, Con A, anti-CD3 monoclonal antibody, or ionomycin in combination with phorbol myristate acetate (PMA). CD4(+) T cells from patients with PBC mediated normal helper function for PWM-stimulated immunoglobulin synthesis at high T/B ratios and their regulatory function was similar to that of normal CD4(+) T cells that had been irradiated to inactivate their suppressor activity. When CD4(+) T cells from patients with PBC were precultured with the combination of Con A and PMA, they mediated potent inhibitory activity similar to that of normal CD4(+) T cells. Thus; CD4(+), Leu-8(+) T cells from patients with PBC have a defect of proliferation and suppressor function that is reversed by coculture with PMA. This finding suggests that impairment of a PMA-inducible lymphocyte activation pathway contributes to abnormal lymphocyte function in PBC.