GERMINAL CENTER DESTRUCTION AS A MAJOR PATHWAY OF HIV PATHOGENESIS

Human immunodeficiency virus (HIV)-induced destruction of follicular d endritic cells (FDCs), which are important in immunological memory, ma y be a major pathway of HIV pathogenesis. We use a mathematical model to investigate this hypothesis and conclude that a low level of FDC de struction could ultimately result in loss of control of HIV. Their slo w turnover makes them good candidates for the part of the immune syste m that fails during the long period of HIV infection. As FDC destructi on is essentially a misdirected immune response, too much immunotherap y may be detrimental. Our model shows how to estimate this critical le vel of immunotherapy. We derive an expression for the time taken to th e loss of immune control. Transient changes in the viral growth rate b efore the immune system fails do not affect this time, providing a pos sible explanation for the results of the Concorde trial. We suggest th at inducible B cell function is a good potential marker of disease pro gression, indicating the functional ability of the FDC network. Finall y, 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.