New research hypotheses in the immunopathogenesis of human immunodeficiency virus infection

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Abstract

The acquired immunodeficiency syndrome (AIDS) is a clinically multifaceted disease induced by infection with the human immunodeficiency virus (HIV). HIV infection results in a complex pattern of immunologic alterations that leads to the development of acquired immunodeficiency syndrome (AIDS) in the majority of HIV seropositive (HIV+) individuals. The reduction in CD4 T lymphocyte counts is the hallmark of HIV infection nevertheless, long before the reduction in CD4 counts reaches critical levels, a series of profound and complex defects that impair the function of CD4 T lymphocytes can be observed. Thus, HIV infection is characterised by quantitative and qualitative defects affecting CD4 T lymphocytes. It was recently suggested that the qualitative defects observed in HIV infection preferentially impair the production of type 1 cytokines, thus provoking abnormalities that selectively affect cell mediated immunity (CMI). Because the efficacy of CMI and humoral immunity is in a continuous reciprocal balance, the impairment of type 1 cytokines production and CMI is likely to be associated with an increased production of type 2 cytokines and an exaggerated stimulation of humoral immunity. Corollaries of this hypothesis are that: 1) a strong cell mediated immunity is more protective in preventing the progression of HIV infection to AIDS; and 2) signs of hyper/abnormal activation of humoral response are indicators of poor prognosis. Additionally, it was recently suggested that programmed cell death (PCD) is an important mechanism leading to CD4 depletion in HIV infection, and that susceptibility of peripheral lymphocytes to PCD appears to be differentially regulated by diverse cytokines. Thus, type 1 cytokines would protect CD4 lymphocytes against PCD, whereas type 2 cytokines would not protect against, and could augment, PCD. We will summarise these and other recent data, and will present some of the latest avenues of research in the immunopathogenesis of HIV infection. Finally, we will discuss some data dealing with the problem of the pathogenesis of HIV infection in the attempt to reconciliate two different visions, the first one which holds the virus itself as the only culprit, and the second one which considers HIV infection as a prototypical immunologic disease or, mimicking a well famous title of an article which was published in the magazine Science: 'It's the virus, stupid (or maybe not)'.

Original languageEnglish
Pages (from-to)163-168
Number of pages6
JournalQuarterly Journal of Nuclear Medicine
Volume39
Issue number3
Publication statusPublished - 1995

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Keywords

  • AIDS
  • HIV infection

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

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