Document 0232
 DOCN  M9440232
 TI    Germinal centre destruction as a major pathway of HIV pathogenesis.
 DT    9404
 AU    Frost SD; McLean AR; Department of Zoology, University of Oxford, United
       Kingdom.
 SO    J Acquir Immune Defic Syndr. 1994 Mar;7(3):236-44. Unique Identifier :
       AIDSLINE MED/94149557
 AB    Human immunodeficiency virus (HIV)-induced destruction of follicular
       dendritic cells (FDCs), which are important in immunological memory, may
       be a major pathway of HIV pathogenesis. We use a mathematical model to
       investigate this hypothesis and conclude that a low level of FDC
       destruction could ultimately result in loss of control of HIV. Their
       slow turnover makes them good candidates for the part of the immune
       system that fails during the long period of HIV infection. As FDC
       destruction is essentially a misdirected immune response, too much
       immunotherapy may be detrimental. Our model shows how to estimate this
       critical level of immunotherapy. We derive an expression for the time
       taken to the loss of immune control. Transient changes in the viral
       growth rate before the immune system fails do not affect this time,
       providing a possible explanation for the results of the Concorde trial.
       We suggest that inducible B cell function is a good potential marker of
       disease progression, indicating the functional ability of the FDC
       network. Finally, we rereview data in the light of the FDC theory,
       paying particular attention to data on CD4+ numbers and function that
       are inconsistent with the classical view of HIV pathogenesis.
 DE    Antigen-Presenting Cells/IMMUNOLOGY/MICROBIOLOGY/PATHOLOGY  Autolysis
       Comparative Study  Dendritic Cells/IMMUNOLOGY/MICROBIOLOGY/*PATHOLOGY
       Human  HIV Infections/*ETIOLOGY/IMMUNOLOGY/PATHOLOGY  Immunologic Memory
       Lymph Nodes/IMMUNOLOGY/MICROBIOLOGY/*PATHOLOGY  Lymphocyte
       Transformation  Mathematics  Models, Biological  Support, Non-U.S. Gov't
       T-Lymphocytes, Suppressor-Effector/IMMUNOLOGY  Time Factors  T4
       Lymphocytes/IMMUNOLOGY/MICROBIOLOGY/PATHOLOGY  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).