HIV INDUCES THYMUS DEPLETION INVIVO

HUMAN immunodeficiency virus (HIV) disease is typified by declining CD 4+ T lymphocyte counts in the peripheral circulation, a loss which may be secondary to accelerated destruction, to suppressed differentiatio n, and/or to sequestration of circulating cells into tissue spaces. As it is hard to distinguish between these possibilities in human subjec ts, the pathogenic mechanisms associated with HIV infection are unclea r. In particular, little is known about the events that occur within i nfected lymphoid organs in which most CD4 T lymphocytes mature and fun ction1,2. To obtain a better description of HIV pathogenesis in vivo, we have implanted human haematolymphoid organs into the immunodeficien t SCID mouse to create the SCID-hu mouse3,4. We have previously shown that these organ systems promote long-term multilineage human haematop oiesis and are permissive for infection with HIV5,6. Here we report th at human thymopoiesis is suppressed by HIV infection, thereby precludi ng regeneration of the peripheral T-cell compartment.