Distinct rate and patterns of human CD4+ T-cell depletion in hu-PBL-SCID mice infected with different isolates of the human immunodeficiency virus.

The most fundamental question about infection with the human immunodeficiency virus is the mechanism by which infection leads to depletion of CD4+ T lymphocytes, a critical cell type for the regulation of both cellular and humoral immunity. We have studied this issue using a unique small-animal model that is highly susceptible to infection with human immunodeficiency virus. Severe combined immune deficient mice are transplanted with human peripheral blood leukocytes to create hu-PBL-SCID mice, which maintain human T and B lymphocytes and some elements of functional immunity. The hu-PBL-SCID mice respond to human immune deficiency virus infection by the relatively rapid loss of human CD4+ T cells, while other human cells remain unaffected. In this paper, we review evidence showing that different isolates of human immunodeficiency virus-2 cause different rates of CD4+ T-cell depletion and that these rates reflect differences in local spread of infection with lymphoid organs.