NOVEL ROLE OF HUMAN CD4 MOLECULE IDENTIFIED IN NEURODEGENERATION

The human CD4 molecule (hCD4) is expressed on T lymphocytes and macrop hages and acts as a key component of the cellular receptor for HIV. At baseline, hCD4 transgenic mice expressed hCD4 on microglia, the resid ent mononuclear phagocytes of the brain, and showed no neuronal damage . Activation of brain microglia by peripheral immune challenges elicit ed neurodegeneration in hCD4 mice but not in nontransgenic controls. I n post-mortem brain tissues from AIDS patients with opportunistic infe ctions, but without typical HIV encephalitis, hCD4 expression correlat ed with neurodegeneration. We conclude that hCD4 may function as an im portant mediator of indirect neuronal damage in infectious and immune- mediated diseases of the central nervous system.