Immunological dysregulation of lymph nodes in AIDS patients

Abstract

Changes in immune competent tissues of the HIV-1-infected person reflect to a certain extent the kind and intensity of immunological dysregulations. The diagnostic approach, however, must include immunophenotyping of cells, immunovirological studies of virus distribution in diseased tissues, and functional tests in addition to classical morphology. The latter technique alone just serves as a crude screening method since structural lesions in lymphoid tissues do not permit discrimination from other HIV-independent immune deficiency and autoimmune disorders. Although the overall appearance of lymph nodes in HIV infection and in chronic autoimmune disorders, such as collagen vascular diseases (e.g., rheumatoid arthritis and systemic lupus erythematosus), is similar, immunophenotyping shows a progressive loss of CD4 cells in HIV infection yet a quantitative increase in this cell population in autoimmune disorders (Krueger 1985a). In addition, there are other persistent active infections by lymphotropic viruses (e.g., EBV or HHV-6) which can cause structural and cellular changes in lymphoid tissues closely resembling HIV-induced lesions (Krueger et al. 1988b; Krueger 1985b). The pathological diagnosis therefore nedds to be supplemented by serological studies and--in selected cases--by in situ hybridization for the demonstration of viral genome. Southern blotting for viral DNA can only detect high numbers of viral genome copies in tissue extracts, not in which cell population the virus resides (e.g., malignant cells vs associated "normal" cells), while the polymerase chain amplification reaction, the most sensitive of all (Buchbinder et al. 1988), cannot yet differentiate between latent and (disease-related) active infection. Taking into consideration the above-described precautions in the evaluation of lymphatic lesions, there are a number of characteristic changes which reflect well the sequelae of HIV infection itself and of the ensuing immune dysregulation. Progressive loss of CD4 cells in the paracortex of lymph nodes and in the peripheral blood leads to inversion of the CD4/CD8 ratio. Loss of demonstrable CD4 cells is probably the consequence not only of cell lysis by HIV-1 infection (note: discrepancy between HIV-1 genome positive cell numbers and depletion of CD4 cells) but also of decreased CD4 marker synthesis in infected cells (Stevenson et al. 1987). In this context it is interesting that Fouchard et al. (1986) were able to show HIV expression in CD8 cells and theorized that these developed from infected CD4 cells which subsequently lost the CD4 epitope and expressed CD8.(ABSTRACT TRUNCATED AT 400 WORDS)