Novel role of human CD4 molecule identified in neurodegeneration

Nat Med. 1998 Apr;4(4):441-6. doi: 10.1038/nm0498-441.


The human CD4 molecule (hCD4) is expressed on T lymphocytes and macrophages and acts as a key component of the cellular receptor for HIV. At baseline, hCD4 transgenic mice expressed hCD4 on microglia, the resident mononuclear phagocytes of the brain, and showed no neuronal damage. Activation of brain microglia by peripheral immune challenges elicited neurodegeneration in hCD4 mice but not in nontransgenic controls. In post-mortem brain tissues from AIDS patients with opportunistic infections, but without typical HIV encephalitis, hCD4 expression correlated with neurodegeneration. We conclude that hCD4 may function as an important mediator of indirect neuronal damage in infectious and immune-mediated diseases of the central nervous system.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • AIDS-Related Opportunistic Infections / immunology*
  • AIDS-Related Opportunistic Infections / pathology*
  • Animals
  • Antigens, CD / biosynthesis
  • Antigens, CD / genetics
  • Antigens, CD / physiology*
  • Brain / immunology*
  • Brain / pathology
  • CD4 Antigens / biosynthesis
  • CD4 Antigens / genetics
  • CD4 Antigens / physiology*
  • Heterozygote
  • Homozygote
  • Humans
  • Inflammation
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred Strains
  • Mice, Transgenic
  • Microglia / immunology*
  • Microglia / pathology
  • Neocortex / immunology
  • Neocortex / pathology
  • Nerve Degeneration / immunology*
  • Nerve Degeneration / pathology
  • Synapses / pathology


  • Antigens, CD
  • CD4 Antigens