CD4+ T-Cell Depletion In Hiv Infection: Mechanisms Of Immunological Failure

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135 Citations (Scopus)

Abstract

The hallmark of acquired immunodeficiency syndrome (AIDS) pathogenesis is a progressive depletion of CD4+ T-cell populations in close association with progressive impairment of cellular immunity and increasing susceptibility to opportunistic infections (OI). Disease progression in untreated human immunodeficiency virus (HIV) infection can take many years, and it was originally hypothesized to be a consequence of slow, viral-mediated CD4+ T-cell destruction. However, massive CD4+ memory T-cell destruction is now known to occur quite early in infection, almost always without overt immunodeficiency. In most individuals, this initial destruction is countered by CD4+ memory T-cell regeneration that preserves CD4+ T-cell numbers and functions above the threshold associated with overt immunodeficiency. This regeneration, which occurs in the setting of chronic immune activation and immune dysregulation does not, however, restore all functionally important CD4+ T-cell populations and is not stable over the long term. Ultimately, CD4+ memory T-cell homeostasis fails and critical effector populations decline below the level necessary to prevent OI. Thus, the onset of overt immune deficiency appears to be intimately linked with CD4+ memory T-cell dynamics and reflects the complex interplay of direct viral cytopathogenicity and the indirect effects of persistent immune activation on CD4+ memory T-cell proliferation, differentiation, and survival.

Original languageEnglish (US)
Pages (from-to)54-64
Number of pages11
JournalImmunological Reviews
Volume254
Issue number1
DOIs
StatePublished - Jul 2013

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T-Lymphocytes
Infection
Opportunistic Infections
Regeneration
Population
Virus Diseases
Cellular Immunity
Disease Progression
Cell Differentiation
Cell Survival
Acquired Immunodeficiency Syndrome
Homeostasis
Cell Count
Cell Proliferation
HIV

Keywords

  • AIDS
  • CD4 T lymphocytes
  • Central memory
  • Lymphocyte depletion
  • Rhesus macaque

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

CD4+ T-Cell Depletion In Hiv Infection : Mechanisms Of Immunological Failure. / Okoye, Afam; Picker, Louis.

In: Immunological Reviews, Vol. 254, No. 1, 07.2013, p. 54-64.

Research output: Contribution to journalArticle

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