Inhibition of acute in vivo human immunodeficiency virus infection by human interleukin 10 treatment of SCID mice implanted with human fetal thymus and liver

被引:42
作者
Kollmann, TR
PettoelloMantovani, M
Katopodis, NF
Hachamovitch, M
Rubinstein, A
Kim, A
Goldstein, H
机构
[1] YESHIVA UNIV ALBERT EINSTEIN COLL MED, DEPT MICROBIOL & IMMUNOL, BRONX, NY 10461 USA
[2] YESHIVA UNIV ALBERT EINSTEIN COLL MED, DEPT PEDIAT, BRONX, NY 10461 USA
[3] YESHIVA UNIV ALBERT EINSTEIN COLL MED, DEPT OBSTET & GYNECOL, BRONX, NY 10461 USA
关键词
D O I
10.1073/pnas.93.7.3126
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
To improve the usefulness of in vivo models for the investigation of the pathophysiology of human immunodeficiency virus (HIV) infection, we modified the construction of SCID mice implanted with human fetal thymus and liver (thy/liv-SCID-hu mice) so that the peripheral blood of the mice contained significant numbers of human monocytes and T cells, After inoculation with HIV-1(59), a primary patient isolate capable of infecting monocytes and T cells, the modified thy/liv-SCID-hu mice developed disseminated HIV infection that was associated with plasma viremia. The development of plasma viremia and HIV infection in thy/liv-SCID-hu mice inoculated with HIV-1(59) was inhibited by acute treatment with human interleukin (IL) 10 but not with human IL-12. The human peripheral blood mononuclear cells in these modified thy/liv-SCID-hu mice were responsive in vivo to treatment with exogenous cytokines. Human interferon gamma expression in the circulating human peripheral blood mononuclear cells was induced by treatment with IL-12 and inhibited by treatment with IL-10. Thus, these modified thy/liv-SCID-hu mice should prove to be a valuable in vivo model for examining the role of immunomodulatory therapy in modifying HIV infection. Furthermore, our demonstration of the in vivo inhibitory effect of IL-10 on acute HIV infection suggests that further studies may be warranted to evaluate whether there is a role for IL-10 therapy in preventing HIV infection in individuals soon after exposure to HIV such as for children born to HIV-infected mothers.
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页码:3126 / 3131
页数:6
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