Divergent effects of chronic HIV-1 infection on human thymocyte maturation in SCID-hu mice.
We have recently developed a modified SCID-hu mouse model in which the implanted human thymus and liver (hu-thy/liv) and human peripheral T cells become infected with HIV-1 after i.p. inoculation. By using this model, we evaluated the effect of HIV-1 infection on thymic maturation and observed that different HIV-1 strains had divergent effects of thymic maturation. Although minimal effects on continued thymopoiesis in the hu-thy/liv implant were observed after chronic infection with two primary patient isolates, HIV-1(28) and HIV-1(59), and with HIV-1ADA, HIV-1Ba-L, HIV-1JR-CSF, HIV-1JR-FL, and HIV-1SF162, significant thymocyte depletion was detected after infection with HIV-1IIIB and HIV-1RF. Thus, the effect of HIV-1 infection on thymocyte maturation may depend upon the strain of HIV-1 infecting the thymus. Despite the minimal effects on thymopoiesis observed in the hu-thy/liv implanted in SCID-hu mice 6 mo after infection with HIV-1(28), significant changes were seen in the human T cell population circulating in the peripheral blood of these mice. These changes ranged from an inversion of the CD4/CD8 ratio of peripheral human T cells in some SCID-hu mice to the almost complete depletion of peripheral human T cells observed in other SCID-hu mice. Because these effects were associated with the detection of HIV-1 infection of the peripheral human T cells, these modified SCID-hu mice should prove to be a valuable model for investigating the effects of chronic HIV-1 infection on the peripheral human T cell population.
Kollmann
T R
TR
Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461.
Kim
A
A
Pettoello-Mantovani
M
M
Hachamovitch
M
M
Rubinstein
A
A
Goldstein
M M
MM
Goldstein
H
H
D000818:Animals; D016516:CD4-CD8 Ratio; D002454:Cell Differentiation / Q000276:immunology; D004279:DNA, Viral / Q000032:analysis; D016332:Fetal Tissue Transplantation / Q000276:immunology; D005434:Flow Cytometry; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007124:Immunoenzyme Techniques; D016031:Liver Transplantation / Q000276:immunology; D051379:Mice; D016513:Mice, SCID; D016133:Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000166:cytology*; D013950:Thymus Gland / Q000166:cytology* / Q000254:growth & development / Q000637:transplantation / Q000821:virology
D004279:DNA, Viral