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. 1995 Aug;69(8):4737–4745. doi: 10.1128/jvi.69.8.4737-4745.1995

Infection frequency of dendritic cells and CD4+ T lymphocytes in spleens of human immunodeficiency virus-positive patients.

D McIlroy 1, B Autran 1, R Cheynier 1, S Wain-Hobson 1, J P Clauvel 1, E Oksenhendler 1, P Debré 1, A Hosmalin 1
PMCID: PMC189281  PMID: 7609039

Abstract

Dendritic cells (DC) are specialized antigen-presenting leukocytes that are responsible for the activation of naive as well as memory T lymphocytes. If infected by human immunodeficiency virus (HIV), DC may transfer virus to CD4+ lymphocytes. However, the question of whether DC are infected in vivo is controversial. As HIV infection is more active in secondary lymphoid organs than in blood, infection of splenic DC isolated from HIV-seropositive patients was investigated. Splenic DC were first enriched and characterized by flow cytometry from HIV- donors. After direct isolation, they were negative for monocyte and T- and B-lymphocyte markers, negative for CD1a, but positive for major histocompatibility complex class II and CD4. After in vitro maturation, major histocompatibility complex class II expression increased, while CD4 expression was lost. Extensive purification from the spleens of seven HIV+ patients was performed by fluorescence-activated cell sorting. The frequency of cells harboring HIV DNA in purified populations was quantified by limiting-dilution PCR. Directly isolated DC (average, 1/3,000; range, 1/720 to 1/18,000) were in each patient 10 to 100 times less infected than CD4+ T lymphocytes (average, 1/52; range, 1/17 to 1/190). On average, 1/1,450 (1/320 to 1/6,100) unseparated mononuclear splenocytes (containing 5% CD4+ lymphocytes) harbored HIV DNA. In conclusion, in these HIV+ patient spleens, DC seem to be infected, but HIV-DNA positive CD4+ T lymphocytes accounted for the vast majority of infected mononuclear splenocytes.

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Selected References

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  1. Armstrong J. A., Horne R. Follicular dendritic cells and virus-like particles in AIDS-related lymphadenopathy. Lancet. 1984 Aug 18;2(8399):370–372. doi: 10.1016/s0140-6736(84)90540-3. [DOI] [PubMed] [Google Scholar]
  2. Cameron P. U., Forsum U., Teppler H., Granelli-Piperno A., Steinman R. M. During HIV-1 infection most blood dendritic cells are not productively infected and can induce allogeneic CD4+ T cells clonal expansion. Clin Exp Immunol. 1992 May;88(2):226–236. doi: 10.1111/j.1365-2249.1992.tb03066.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Cameron P. U., Freudenthal P. S., Barker J. M., Gezelter S., Inaba K., Steinman R. M. Dendritic cells exposed to human immunodeficiency virus type-1 transmit a vigorous cytopathic infection to CD4+ T cells. Science. 1992 Jul 17;257(5068):383–387. doi: 10.1126/science.1352913. [DOI] [PubMed] [Google Scholar]
  4. Cheynier R., Henrichwark S., Hadida F., Pelletier E., Oksenhendler E., Autran B., Wain-Hobson S. HIV and T cell expansion in splenic white pulps is accompanied by infiltration of HIV-specific cytotoxic T lymphocytes. Cell. 1994 Aug 12;78(3):373–387. doi: 10.1016/0092-8674(94)90417-0. [DOI] [PubMed] [Google Scholar]
  5. Cimarelli A., Zambruno G., Marconi A., Girolomoni G., Bertazzoni U., Giannetti A. Quantitation by competitive PCR of HIV-1 proviral DNA in epidermal Langerhans cells of HIV-infected patients. J Acquir Immune Defic Syndr. 1994 Mar;7(3):230–235. [PubMed] [Google Scholar]
  6. Clerici M., Stocks N. I., Zajac R. A., Boswell R. N., Lucey D. R., Via C. S., Shearer G. M. Detection of three distinct patterns of T helper cell dysfunction in asymptomatic, human immunodeficiency virus-seropositive patients. Independence of CD4+ cell numbers and clinical staging. J Clin Invest. 1989 Dec;84(6):1892–1899. doi: 10.1172/JCI114376. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Delassus S., Cheynier R., Wain-Hobson S. Nonhomogeneous distribution of human immunodeficiency virus type 1 proviruses in the spleen. J Virol. 1992 Sep;66(9):5642–5645. doi: 10.1128/jvi.66.9.5642-5645.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Delorme P., Dezutter-Dambuyant C., Ebersold A., Desgranges C., Thivolet J., Schmitt D. In vitro infection of epidermal Langerhans cells with human immunodeficiency virus type 1 (HTLV-IIIB isolate). Res Virol. 1993 Jan-Feb;144(1):53–58. doi: 10.1016/s0923-2516(06)80012-9. [DOI] [PubMed] [Google Scholar]
  9. Embretson J., Zupancic M., Ribas J. L., Burke A., Racz P., Tenner-Racz K., Haase A. T. Massive covert infection of helper T lymphocytes and macrophages by HIV during the incubation period of AIDS. Nature. 1993 Mar 25;362(6418):359–362. doi: 10.1038/362359a0. [DOI] [PubMed] [Google Scholar]
  10. Fox C. H., Tenner-Rácz K., Rácz P., Firpo A., Pizzo P. A., Fauci A. S. Lymphoid germinal centers are reservoirs of human immunodeficiency virus type 1 RNA. J Infect Dis. 1991 Dec;164(6):1051–1057. doi: 10.1093/infdis/164.6.1051. [DOI] [PubMed] [Google Scholar]
  11. Freudenthal P. S., Steinman R. M. The distinct surface of human blood dendritic cells, as observed after an improved isolation method. Proc Natl Acad Sci U S A. 1990 Oct;87(19):7698–7702. doi: 10.1073/pnas.87.19.7698. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Inaba K., Metlay J. P., Crowley M. T., Steinman R. M. Dendritic cells pulsed with protein antigens in vitro can prime antigen-specific, MHC-restricted T cells in situ. J Exp Med. 1990 Aug 1;172(2):631–640. doi: 10.1084/jem.172.2.631. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Karhumäki E., Viljanen M. E., Cottler-Fox M., Ranki A., Fox C. H., Krohn K. J. An improved enrichment method for functionally competent, highly purified peripheral blood dendritic cells and its application to HIV-infected blood samples. Clin Exp Immunol. 1993 Mar;91(3):482–488. doi: 10.1111/j.1365-2249.1993.tb05928.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Knight S. C., Macatonia S. E. Effect of HIV on antigen presentation by dendritic cells and macrophages. Res Virol. 1991 Mar-Jun;142(2-3):123–128. doi: 10.1016/0923-2516(91)90048-8. [DOI] [PubMed] [Google Scholar]
  15. Langhoff E., Terwilliger E. F., Bos H. J., Kalland K. H., Poznansky M. C., Bacon O. M., Haseltine W. A. Replication of human immunodeficiency virus type 1 in primary dendritic cell cultures. Proc Natl Acad Sci U S A. 1991 Sep 15;88(18):7998–8002. doi: 10.1073/pnas.88.18.7998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Le Tourneau A., Audouin J., Diebold J., Marche C., Tricottet V., Reynes M. LAV-like viral particles in lymph node germinal centers in patients with the persistent lymphadenopathy syndrome and the acquired immunodeficiency syndrome-related complex: an ultrastructural study of 30 cases. Hum Pathol. 1986 Oct;17(10):1047–1053. doi: 10.1016/s0046-8177(86)80089-2. [DOI] [PubMed] [Google Scholar]
  17. Levy J. A. Pathogenesis of human immunodeficiency virus infection. Microbiol Rev. 1993 Mar;57(1):183–289. doi: 10.1128/mr.57.1.183-289.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Macatonia S. E., Lau R., Patterson S., Pinching A. J., Knight S. C. Dendritic cell infection, depletion and dysfunction in HIV-infected individuals. Immunology. 1990 Sep;71(1):38–45. [PMC free article] [PubMed] [Google Scholar]
  19. Macatonia S. E., Taylor P. M., Knight S. C., Askonas B. A. Primary stimulation by dendritic cells induces antiviral proliferative and cytotoxic T cell responses in vitro. J Exp Med. 1989 Apr 1;169(4):1255–1264. doi: 10.1084/jem.169.4.1255. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. O'Doherty U., Steinman R. M., Peng M., Cameron P. U., Gezelter S., Kopeloff I., Swiggard W. J., Pope M., Bhardwaj N. Dendritic cells freshly isolated from human blood express CD4 and mature into typical immunostimulatory dendritic cells after culture in monocyte-conditioned medium. J Exp Med. 1993 Sep 1;178(3):1067–1076. doi: 10.1084/jem.178.3.1067. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Oksenhendler E., Bierling P., Chevret S., Delfraissy J. F., Laurian Y., Clauvel J. P., Seligmann M. Splenectomy is safe and effective in human immunodeficiency virus-related immune thrombocytopenia. Blood. 1993 Jul 1;82(1):29–32. [PubMed] [Google Scholar]
  22. Pantaleo G., Graziosi C., Butini L., Pizzo P. A., Schnittman S. M., Kotler D. P., Fauci A. S. Lymphoid organs function as major reservoirs for human immunodeficiency virus. Proc Natl Acad Sci U S A. 1991 Nov 1;88(21):9838–9842. doi: 10.1073/pnas.88.21.9838. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Pantaleo G., Graziosi C., Demarest J. F., Butini L., Montroni M., Fox C. H., Orenstein J. M., Kotler D. P., Fauci A. S. HIV infection is active and progressive in lymphoid tissue during the clinically latent stage of disease. Nature. 1993 Mar 25;362(6418):355–358. doi: 10.1038/362355a0. [DOI] [PubMed] [Google Scholar]
  24. Patterson S., Gross J., Bedford P., Knight S. C. Morphology and phenotype of dendritic cells from peripheral blood and their productive and non-productive infection with human immunodeficiency virus type 1. Immunology. 1991 Mar;72(3):361–367. [PMC free article] [PubMed] [Google Scholar]
  25. Pope M., Betjes M. G., Romani N., Hirmand H., Cameron P. U., Hoffman L., Gezelter S., Schuler G., Steinman R. M. Conjugates of dendritic cells and memory T lymphocytes from skin facilitate productive infection with HIV-1. Cell. 1994 Aug 12;78(3):389–398. doi: 10.1016/0092-8674(94)90418-9. [DOI] [PubMed] [Google Scholar]
  26. Steinman R. M. The dendritic cell system and its role in immunogenicity. Annu Rev Immunol. 1991;9:271–296. doi: 10.1146/annurev.iy.09.040191.001415. [DOI] [PubMed] [Google Scholar]
  27. Steinman R. M., Witmer M. D. Lymphoid dendritic cells are potent stimulators of the primary mixed leukocyte reaction in mice. Proc Natl Acad Sci U S A. 1978 Oct;75(10):5132–5136. doi: 10.1073/pnas.75.10.5132. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Tenner-Racz K., Racz P., Bofill M., Schulz-Meyer A., Dietrich M., Kern P., Weber J., Pinching A. J., Veronese-Dimarzo F., Popovic M. HTLV-III/LAV viral antigens in lymph nodes of homosexual men with persistent generalized lymphadenopathy and AIDS. Am J Pathol. 1986 Apr;123(1):9–15. [PMC free article] [PubMed] [Google Scholar]
  29. Tenner-Rácz K., Rácz P., Dietrich M., Kern P. Altered follicular dendritic cells and virus-like particles in AIDS and AIDS-related lymphadenopathy. Lancet. 1985 Jan 12;1(8420):105–106. doi: 10.1016/s0140-6736(85)91994-4. [DOI] [PubMed] [Google Scholar]
  30. Thomas R., Davis L. S., Lipsky P. E. Isolation and characterization of human peripheral blood dendritic cells. J Immunol. 1993 Feb 1;150(3):821–834. [PubMed] [Google Scholar]
  31. Tschachler E., Groh V., Popovic M., Mann D. L., Konrad K., Safai B., Eron L., diMarzo Veronese F., Wolff K., Stingl G. Epidermal Langerhans cells--a target for HTLV-III/LAV infection. J Invest Dermatol. 1987 Feb;88(2):233–237. doi: 10.1111/1523-1747.ep12525402. [DOI] [PubMed] [Google Scholar]
  32. Weissman D., Li Y., Ananworanich J., Zhou L. J., Adelsberger J., Tedder T. F., Baseler M., Fauci A. S. Three populations of cells with dendritic morphology exist in peripheral blood, only one of which is infectable with human immunodeficiency virus type 1. Proc Natl Acad Sci U S A. 1995 Jan 31;92(3):826–830. doi: 10.1073/pnas.92.3.826. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Winkel K., Sotzik F., Vremec D., Cameron P. U., Shortman K. CD4 and CD8 expression by human and mouse thymic dendritic cells. Immunol Lett. 1994 May;40(2):93–99. doi: 10.1016/0165-2478(94)90178-3. [DOI] [PubMed] [Google Scholar]
  34. Wood G. S., Warner N. L., Warnke R. A. Anti-Leu-3/T4 antibodies react with cells of monocyte/macrophage and Langerhans lineage. J Immunol. 1983 Jul;131(1):212–216. [PubMed] [Google Scholar]
  35. Wood R., Dong H., Katzenstein D. A., Merigan T. C. Quantification and comparison of HIV-1 proviral load in peripheral blood mononuclear cells and isolated CD4+ T cells. J Acquir Immune Defic Syndr. 1993 Mar;6(3):237–240. [PubMed] [Google Scholar]
  36. Zambruno G., Mori L., Marconi A., Mongiardo N., De Rienzo B., Bertazzoni U., Giannetti A. Detection of HIV-1 in epidermal Langerhans cells of HIV-infected patients using the polymerase chain reaction. J Invest Dermatol. 1991 Jun;96(6):979–982. doi: 10.1111/1523-1747.ep12476469. [DOI] [PubMed] [Google Scholar]
  37. Zinkernagel R. M., Hengartner H. Virally induced immunosuppression. Curr Opin Immunol. 1992 Aug;4(4):408–412. doi: 10.1016/s0952-7915(06)80031-2. [DOI] [PubMed] [Google Scholar]

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