The investigator proposes to extend previous findings in the SCID-hu mouse model of normal human thymopoiesis in which HIV infection causes loss of CD4+ thymocytes and pathology similar to that seen in infected persons.
The Specific Aims to be addresses are: 1) to more completely define the pathogenic mechanisms in operating in human thymocytes, 2) to determine the effects of HIV infection on thymic stromal elements, and 3) to determine the pathogenic potential of attenuated virus strains in vivo. Although thymic functions is most obvious in the developing fetus and in children, the investigator believe that these studies may have relevance to infected adult patients because recent clinical data suggest that naive T lymphocytes can be produced by adults following antiretroviral therapy. The investigator proposes that experiments addressing the pathogenic potential of viral mutants will help identify candidate live attenuated vaccine strains. It is suggested that these studies should further knowledge on the effect of HIV on human hematopoietic organs and help to understand how HIV causes the profound immunosuppression seen in AIDS.
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