title: From HIV infection to AIDS: are the manifestations of effective immune resistance misinterpreted?
abstract: Viewing the immune system as part of an adaptive communication network, rather than merely a coalition of effectors, we argue that the alterations in the immune system that occur in HIV-infected patients, generally considered to be "abnormalities," cannot be attributed directly to deleterious effects of the virus on CD4+ T cells or other particular cells. Rather, many of the functional changes that occur during the asymptomatic phase reflect a normal mode of immune resistance to chronic infection, different from the "stereotypic" immune response, whereby patterns of signals are recognized and classified and evoke selective activities. The relative stability of the virus-host relationship in this phase involves a degree of mutual adaptation. However, an excessively perturbed microenvironment is the core of unstable cellular organization in which the resistance to infection gradually deteriorates. We suggest that this is due to "overadaptation" of lymphocytes and accessory cells to the infectious agent(s). We further speculate that a key factor underlying this process is a reduced rate of replacement of CD4+ T cells, which are sequestered at the sites of infection, by fresh unprimed or memory T cells. Direct and local viral effects are amplified and propagated by "affected" cells, which are not necessarily infected. The collective profile of gene expression in various types of affected cells might adequately reflect tissue organization and the overall functional status of the immune system and thus could serve as a guide to therapy. This would require collection of a more extensive array of immunologic data than is now gathered, and novel approaches to analyzing such data.
authors.affiliation: Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel Aviv University, Israel.
authors.forename: Z
authors.initials: Z
authors.lastname: Grossman
authors.forename: Z
authors.initials: Z
authors.lastname: Bentwich
authors.forename: R B
authors.initials: RB
authors.lastname: Herberman
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000209:etiology* / Q000276:immunology; D002908:Chronic Disease; D006678:HIV / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D007113:Immunity, Innate; D008214:Lymphocytes / Q000276:immunology