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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

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Abstract

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.

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Author notes

  1. Ricardo Moreno-Otero MD

    Present address: Unit of Hepatology, Hospital de la Princesa, Autonomous University of Madrid, Spain

  2. Marjorie E. Kanof MD

    Present address: Pediatric Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts

  3. María P. Civeira MD

    Present address: Department of Internal Medicine, University of Navarra, Spain

Authors and Affiliations

  1. From the Liver Diseases Section, Digestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, and the Mucosal Immunity Section, Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland

    Ricardo Moreno-Otero MD, Yoko Murakawa PhD,  Marjorie E. Kanof MD,  María P. Civeira MD, E. Anthony Jones MD & Stephen P. James MD

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  1. Ricardo Moreno-Otero MD
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  2. Yoko Murakawa PhD
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  3. Marjorie E. Kanof MD
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  4. María P. Civeira MD
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  5. E. Anthony Jones MD
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  6. Stephen P. James MD
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Moreno-Otero, R., Murakawa, Y., Kanof, M.E. et al. Defective proliferation and regulatory function of CD4+ T cells bearing Leu-8 homing receptor in primary biliary cirrhosis. Digest Dis Sci 39, 1329–1336 (1994). https://doi.org/10.1007/BF02093801

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  • DOI: https://doi.org/10.1007/BF02093801

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