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.
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.
Moreno-Otero
R
R
Liver Diseases Section, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, Maryland.
Murakawa
Y
Y
Kanof
M E
ME
Civeira
M P
MP
Jones
E A
EA
James
S P
SP
D000328:Adult; D000368:Aged; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology*; D015815:Cell Adhesion Molecules / Q000032:analysis*; D002469:Cell Separation; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D019041:L-Selectin; D008105:Liver Cirrhosis, Biliary / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis*; D008875:Middle Aged; D016201:Receptors, Lymphocyte Homing / Q000032:analysis*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D015815:Cell Adhesion Molecules; D008562:Membrane Glycoproteins; D016201:Receptors, Lymphocyte Homing; D019041:L-Selectin; D013755:Tetradecanoylphorbol Acetate