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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1996 Apr 2;93(7):3126–3131. doi: 10.1073/pnas.93.7.3126

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

T R Kollmann 1, M Pettoello-Mantovani 1, N F Katopodis 1, M Hachamovitch 1, A Rubinstein 1, A Kim 1, H Goldstein 1
PMCID: PMC39773  PMID: 8610180

Abstract

To improve the usefulness of in vivo mode 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 to in vivo 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 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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Selected References

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  1. Akridge R. E., Oyafuso L. K., Reed S. G. IL-10 is induced during HIV-1 infection and is capable of decreasing viral replication in human macrophages. J Immunol. 1994 Dec 15;153(12):5782–5789. [PubMed] [Google Scholar]
  2. Chan S. H., Perussia B., Gupta J. W., Kobayashi M., Pospísil M., Young H. A., Wolf S. F., Young D., Clark S. C., Trinchieri G. Induction of interferon gamma production by natural killer cell stimulatory factor: characterization of the responder cells and synergy with other inducers. J Exp Med. 1991 Apr 1;173(4):869–879. doi: 10.1084/jem.173.4.869. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Chernoff A. E., Granowitz E. V., Shapiro L., Vannier E., Lonnemann G., Angel J. B., Kennedy J. S., Rabson A. R., Wolff S. M., Dinarello C. A. A randomized, controlled trial of IL-10 in humans. Inhibition of inflammatory cytokine production and immune responses. J Immunol. 1995 May 15;154(10):5492–5499. [PubMed] [Google Scholar]
  4. Coffin J. M. HIV population dynamics in vivo: implications for genetic variation, pathogenesis, and therapy. Science. 1995 Jan 27;267(5197):483–489. doi: 10.1126/science.7824947. [DOI] [PubMed] [Google Scholar]
  5. D'Andrea A., Aste-Amezaga M., Valiante N. M., Ma X., Kubin M., Trinchieri G. Interleukin 10 (IL-10) inhibits human lymphocyte interferon gamma-production by suppressing natural killer cell stimulatory factor/IL-12 synthesis in accessory cells. J Exp Med. 1993 Sep 1;178(3):1041–1048. doi: 10.1084/jem.178.3.1041. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Foli A., Saville M. W., Baseler M. W., Yarchoan R. Effects of the Th1 and Th2 stimulatory cytokines interleukin-12 and interleukin-4 on human immunodeficiency virus replication. Blood. 1995 Apr 15;85(8):2114–2123. [PubMed] [Google Scholar]
  7. Ho D. D., Neumann A. U., Perelson A. S., Chen W., Leonard J. M., Markowitz M. Rapid turnover of plasma virions and CD4 lymphocytes in HIV-1 infection. Nature. 1995 Jan 12;373(6510):123–126. doi: 10.1038/373123a0. [DOI] [PubMed] [Google Scholar]
  8. Kollmann T. R., Kim A., Pettoello-Mantovani M., Hachamovitch M., Rubinstein A., Goldstein M. M., Goldstein H. Divergent effects of chronic HIV-1 infection on human thymocyte maturation in SCID-hu mice. J Immunol. 1995 Jan 15;154(2):907–921. [PubMed] [Google Scholar]
  9. Kollmann T. R., Kim A., Zhuang X., Hachamovitch M., Goldstein H. Reconstitution of SCID mice with human lymphoid and myeloid cells after transplantation with human fetal bone marrow without the requirement for exogenous human cytokines. Proc Natl Acad Sci U S A. 1994 Aug 16;91(17):8032–8036. doi: 10.1073/pnas.91.17.8032. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Kollmann T. R., Pettoello-Mantovani M., Zhuang X., Kim A., Hachamovitch M., Smarnworawong P., Rubinstein A., Goldstein H. Disseminated human immunodeficiency virus 1 (HIV-1) infection in SCID-hu mice after peripheral inoculation with HIV-1. J Exp Med. 1994 Feb 1;179(2):513–522. doi: 10.1084/jem.179.2.513. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Kootstra N. A., van 't Wout A., Huisman H. G., Miedema F., Schuitemaker H. Interference of interleukin-10 with human immunodeficiency virus type 1 replication in primary monocyte-derived macrophages. J Virol. 1994 Nov;68(11):6967–6975. doi: 10.1128/jvi.68.11.6967-6975.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Krowka J. F., Sarin S., Namikawa R., McCune J. M., Kaneshima H. Human T cells in the SCID-hu mouse are phenotypically normal and functionally competent. J Immunol. 1991 Jun 1;146(11):3751–3756. [PubMed] [Google Scholar]
  13. Kubin M., Kamoun M., Trinchieri G. Interleukin 12 synergizes with B7/CD28 interaction in inducing efficient proliferation and cytokine production of human T cells. J Exp Med. 1994 Jul 1;180(1):211–222. doi: 10.1084/jem.180.1.211. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Montaner L. J., Griffin P., Gordon S. Interleukin-10 inhibits initial reverse transcription of human immunodeficiency virus type 1 and mediates a virostatic latent state in primary blood-derived human macrophages in vitro. J Gen Virol. 1994 Dec;75(Pt 12):3393–3400. doi: 10.1099/0022-1317-75-12-3393. [DOI] [PubMed] [Google Scholar]
  15. Moore K. W., O'Garra A., de Waal Malefyt R., Vieira P., Mosmann T. R. Interleukin-10. Annu Rev Immunol. 1993;11:165–190. doi: 10.1146/annurev.iy.11.040193.001121. [DOI] [PubMed] [Google Scholar]
  16. Namikawa R., Kaneshima H., Lieberman M., Weissman I. L., McCune J. M. Infection of the SCID-hu mouse by HIV-1. Science. 1988 Dec 23;242(4886):1684–1686. doi: 10.1126/science.3201256. [DOI] [PubMed] [Google Scholar]
  17. Namikawa R., Weilbaecher K. N., Kaneshima H., Yee E. J., McCune J. M. Long-term human hematopoiesis in the SCID-hu mouse. J Exp Med. 1990 Oct 1;172(4):1055–1063. doi: 10.1084/jem.172.4.1055. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Saville M. W., Taga K., Foli A., Broder S., Tosato G., Yarchoan R. Interleukin-10 suppresses human immunodeficiency virus-1 replication in vitro in cells of the monocyte/macrophage lineage. Blood. 1994 Jun 15;83(12):3591–3599. [PubMed] [Google Scholar]
  19. Schuitemaker H., Koot M., Kootstra N. A., Dercksen M. W., de Goede R. E., van Steenwijk R. P., Lange J. M., Schattenkerk J. K., Miedema F., Tersmette M. Biological phenotype of human immunodeficiency virus type 1 clones at different stages of infection: progression of disease is associated with a shift from monocytotropic to T-cell-tropic virus population. J Virol. 1992 Mar;66(3):1354–1360. doi: 10.1128/jvi.66.3.1354-1360.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Wang P., Wu P., Siegel M. I., Egan R. W., Billah M. M. IL-10 inhibits transcription of cytokine genes in human peripheral blood mononuclear cells. J Immunol. 1994 Jul 15;153(2):811–816. [PubMed] [Google Scholar]
  21. Wei X., Ghosh S. K., Taylor M. E., Johnson V. A., Emini E. A., Deutsch P., Lifson J. D., Bonhoeffer S., Nowak M. A., Hahn B. H. Viral dynamics in human immunodeficiency virus type 1 infection. Nature. 1995 Jan 12;373(6510):117–122. doi: 10.1038/373117a0. [DOI] [PubMed] [Google Scholar]
  22. Weissman D., Poli G., Fauci A. S. Interleukin 10 blocks HIV replication in macrophages by inhibiting the autocrine loop of tumor necrosis factor alpha and interleukin 6 induction of virus. AIDS Res Hum Retroviruses. 1994 Oct;10(10):1199–1206. doi: 10.1089/aid.1994.10.1199. [DOI] [PubMed] [Google Scholar]
  23. Wu C. Y., Demeure C., Kiniwa M., Gately M., Delespesse G. IL-12 induces the production of IFN-gamma by neonatal human CD4 T cells. J Immunol. 1993 Aug 15;151(4):1938–1949. [PubMed] [Google Scholar]
  24. van't Wout A. B., Kootstra N. A., Mulder-Kampinga G. A., Albrecht-van Lent N., Scherpbier H. J., Veenstra J., Boer K., Coutinho R. A., Miedema F., Schuitemaker H. Macrophage-tropic variants initiate human immunodeficiency virus type 1 infection after sexual, parenteral, and vertical transmission. J Clin Invest. 1994 Nov;94(5):2060–2067. doi: 10.1172/JCI117560. [DOI] [PMC free article] [PubMed] [Google Scholar]

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