Defective proliferation and regulatory function of CD4+ T cells bearing Leu-8 homing receptor in primary biliary cirrhosis. Phorbol myristate acetate enhances T-cell function
Moreno-Otero R, Murakawa Y, Kanof ME, Civeira MP, Jones EA, James SP.
Liver Diseases Section, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, Maryland.
The majority of circulating CD4+ T cells express the Leu-8 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.
CITATION Dig Dis Sci. 1994 Jun;39(6):1329-36