HUMAN-IMMUNODEFICIENCY-VIRUS INFECTION OF THE HUMAN THYMUS AND DISRUPTION OF THE THYMIC MICROENVIRONMENT IN THE SCID-HU MOUSE

Infection with the human immunodeficiency virus (HIV) results in immun osuppression and depletion of circulating CD4+ T cells. Since the thym us is the primary organ in which T cells mature it is of interest to e xamine the effects of HIV infection in this tissue. HIV infection has been demonstrated in the thymuses of infected individuals and thymocyt es have been previously demonstrated to be susceptible to HIV infectio n both in vivo, using the SCID-hu mouse, and in vitro. The present stu dy sought to determine which subsets of thymocytes were infected in th e SCID-hu mouse model and to evaluate HIV-related alterations in the t hymic microenvironment. Using two different primary HIV isolates, infe ction was found in CD4+/CD8+ double positive thymocytes as well as in both the CD4+ and CD8+ single positive subsets of thymocytes. The kine tics of infection and resulting viral burden differed among the three thymocyte subsets and depended on which HIV isolate was used for infec tion. Thymic epithelial (TE) cells were also shown to endocytose virus and to often contain copious amounts of viral RNA in the cytoplasm by in situ hybridization, although productive infection of these cells c ould not be definitively shown. Furthermore, degenerating TE cells wer e observed even without detection of HIV in the degenerating cells. Tw o striking morphologic patterns of infection were seen, involving eith er predominantly thymocyte infection and depletion, or TE cell involve ment with detectable cytoplasmic viral RNA and/or TE cell toxicity. Th us, a variety of cells in the human thymus is susceptible to HIV infec tion, and infection with HIV results in a marked disruption of the thy mic microenvironment leading to depletion of thymocytes and degenerati on of TE cells.