Skip to main content
Clinical and Diagnostic Laboratory Immunology logoLink to Clinical and Diagnostic Laboratory Immunology
. 1995 May;2(3):343–348. doi: 10.1128/cdli.2.3.343-348.1995

Interaction of human immunodeficiency virus type 1, human T-cell leukemia/lymphoma virus type I (HTLV-I), and HTLV-II with in vitro-generated dendritic cells.

D Zucker-Franklin 1, M Fraig 1, G Grusky 1
PMCID: PMC170157  PMID: 7664181

Abstract

Although it is known that impairment of dendritic cells (DC) plays a role in the pathogenesis and immunosuppression of retrovirus-associated diseases, it is not clear whether, or to what extent, these antigen-presenting cells themselves become infected. The realization that the cells can be generated in vitro in larger numbers than can be isolated from circulating blood or bone marrow raised the possibility that they could be used for therapeutic purposes. Therefore, we investigated whether DC generated in vitro from CD34 precursors are susceptible to infection when cocultured with human immunodeficiency virus type 1- or human T-cell leukemia/lymphoma virus-infected cell lines. While there appears to be a remarkable affinity of the viruses for the plasma membranes of the DC, interiorization or budding was not observed in 30 experiments carried out under a variety of conditions.

Full Text

The Full Text of this article is available as a PDF (1.7 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bani D., Pimpinelli N., Moretti S., Giannotti B. Langerhans cells and mycosis fungoides--a critical overview of their pathogenic role in the disease. Clin Exp Dermatol. 1990 Jan;15(1):7–12. doi: 10.1111/j.1365-2230.1990.tb02009.x. [DOI] [PubMed] [Google Scholar]
  2. Braathen L. R., Ramirez G., Kunze R. O., Mork C., Strand O. Latent infection of epidermal Langerhans cells in HIV-positive individuals. Res Virol. 1991 Mar-Jun;142(2-3):119–121. doi: 10.1016/0923-2516(91)90047-7. [DOI] [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. Caux C., Dezutter-Dambuyant C., Schmitt D., Banchereau J. GM-CSF and TNF-alpha cooperate in the generation of dendritic Langerhans cells. Nature. 1992 Nov 19;360(6401):258–261. doi: 10.1038/360258a0. [DOI] [PubMed] [Google Scholar]
  5. Cerio R., Griffiths C. E., Cooper K. D., Nickoloff B. J., Headington J. T. Characterization of factor XIIIa positive dermal dendritic cells in normal and inflamed skin. Br J Dermatol. 1989 Oct;121(4):421–431. doi: 10.1111/j.1365-2133.1989.tb15509.x. [DOI] [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. Eales L. J., Farrant J., Helbert M., Pinching A. J. Peripheral blood dendritic cells in persons with AIDS and AIDS related complex: loss of high intensity class II antigen expression and function. Clin Exp Immunol. 1988 Mar;71(3):423–427. [PMC free article] [PubMed] [Google Scholar]
  8. 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]
  9. Flechner E. R., Freudenthal P. S., Kaplan G., Steinman R. M. Antigen-specific T lymphocytes efficiently cluster with dendritic cells in the human primary mixed-leukocyte reaction. Cell Immunol. 1988 Jan;111(1):183–195. doi: 10.1016/0008-8749(88)90062-7. [DOI] [PubMed] [Google Scholar]
  10. Flotte T. J., Springer T. A., Thorbecke G. J. Dendritic cell and macrophage staining by monoclonal antibodies in tissue sections and epidermal sheets. Am J Pathol. 1983 Apr;111(1):112–124. [PMC free article] [PubMed] [Google Scholar]
  11. 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]
  12. Francotte M., Urbain J. Enhancement of antibody response by mouse dendritic cells pulsed with tobacco mosaic virus or with rabbit antiidiotypic antibodies raised against a private rabbit idiotype. Proc Natl Acad Sci U S A. 1985 Dec;82(23):8149–8152. doi: 10.1073/pnas.82.23.8149. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Giannetti A., Zambruno G., Cimarelli A., Marconi A., Negroni M., Girolomoni G., Bertazzoni U. Direct detection of HIV-1 RNA in epidermal Langerhans cells of HIV-infected patients. J Acquir Immune Defic Syndr. 1993 Apr;6(4):329–333. [PubMed] [Google Scholar]
  14. Hanaoka M. Progress in adult T cell leukemia research. Acta Pathol Jpn. 1982;32 (Suppl 1):171–185. [PubMed] [Google Scholar]
  15. Hengel H., Lindner M., Wagner H., Heeg K. Frequency of herpes simplex virus-specific murine cytotoxic T lymphocyte precursors in mitogen- and antigen-driven primary in vitro T cell responses. J Immunol. 1987 Dec 15;139(12):4196–4202. [PubMed] [Google Scholar]
  16. 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]
  17. Kast W. M., Boog C. J., Roep B. O., Voordouw A. C., Melief C. J. Failure or success in the restoration of virus-specific cytotoxic T lymphocyte response defects by dendritic cells. J Immunol. 1988 May 1;140(9):3186–3193. [PubMed] [Google Scholar]
  18. 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]
  19. Kornbluth R. S., McCutchan J. A. Skin test responses as predictors of tuberculous infection and of progression in HIV-infected persons. Ann Intern Med. 1993 Aug 1;119(3):241–243. doi: 10.7326/0003-4819-119-3-199308010-00011. [DOI] [PubMed] [Google Scholar]
  20. LaGrenade L., Hanchard B., Fletcher V., Cranston B., Blattner W. Infective dermatitis of Jamaican children: a marker for HTLV-I infection. Lancet. 1990 Dec 1;336(8727):1345–1347. doi: 10.1016/0140-6736(90)92896-p. [DOI] [PubMed] [Google Scholar]
  21. Langhoff E., Steinman R. M. Clonal expansion of human T lymphocytes initiated by dendritic cells. J Exp Med. 1989 Jan 1;169(1):315–320. doi: 10.1084/jem.169.1.315. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. 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]
  23. Li C. Y., Lam K. W., Yam L. T. Esterases in human leukocytes. J Histochem Cytochem. 1973 Jan;21(1):1–12. doi: 10.1177/21.1.1. [DOI] [PubMed] [Google Scholar]
  24. MacKie R. M. Initial event in mycosis fungoides of the skin is viral infection of epidermal Langerhans cells. Lancet. 1981 Aug 8;2(8241):283–285. doi: 10.1016/s0140-6736(81)90529-8. [DOI] [PubMed] [Google Scholar]
  25. 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]
  26. Newton R. C., Limpuangthip P., Greenberg S., Gam A., Neva F. A. Strongyloides stercoralis hyperinfection in a carrier of HTLV-I virus with evidence of selective immunosuppression. Am J Med. 1992 Feb;92(2):202–208. doi: 10.1016/0002-9343(92)90113-p. [DOI] [PubMed] [Google Scholar]
  27. Pancake B. A., Zucker-Franklin D., Coutavas E. E. The cutaneous T cell lymphoma, mycosis fungoides, is a human T cell lymphotropic virus-associated disease. A study of 50 patients. J Clin Invest. 1995 Feb;95(2):547–554. doi: 10.1172/JCI117697. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Pancake B. A., Zucker-Franklin D. HTLV tax and mycosis fungoides. N Engl J Med. 1993 Aug 19;329(8):580–580. doi: 10.1056/NEJM199308193290816. [DOI] [PubMed] [Google Scholar]
  29. 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]
  30. Pantaleo G., Graziosi C., Fauci A. S. The role of lymphoid organs in the pathogenesis of HIV infection. Semin Immunol. 1993 Jun;5(3):157–163. doi: 10.1006/smim.1993.1019. [DOI] [PubMed] [Google Scholar]
  31. Patey O., Gessain A., Breuil J., Courillon-Mallet A., Daniel M. T., Miclea J. M., Roucayrol A. M., Sigaux F., Lafaix C. Seven years of recurrent severe strongyloidiasis in an HTLV-I-infected man who developed adult T-cell leukaemia. AIDS. 1992 Jun;6(6):575–579. doi: 10.1097/00002030-199206000-00009. [DOI] [PubMed] [Google Scholar]
  32. Patterson S., Knight S. C. Susceptibility of human peripheral blood dendritic cells to infection by human immunodeficiency virus. J Gen Virol. 1987 Apr;68(Pt 4):1177–1181. doi: 10.1099/0022-1317-68-4-1177. [DOI] [PubMed] [Google Scholar]
  33. Popovic M., Sarin P. S., Robert-Gurroff M., Kalyanaraman V. S., Mann D., Minowada J., Gallo R. C. Isolation and transmission of human retrovirus (human t-cell leukemia virus). Science. 1983 Feb 18;219(4586):856–859. doi: 10.1126/science.6600519. [DOI] [PubMed] [Google Scholar]
  34. Rowden G., Lewis M. G. Langerhans cells: involvement in the pathogenesis of mycosis fungoides. Br J Dermatol. 1976 Dec;95(6):665–672. doi: 10.1111/j.1365-2133.1976.tb07044.x. [DOI] [PubMed] [Google Scholar]
  35. Santiago-Schwarz F., Belilos E., Diamond B., Carsons S. E. TNF in combination with GM-CSF enhances the differentiation of neonatal cord blood stem cells into dendritic cells and macrophages. J Leukoc Biol. 1992 Sep;52(3):274–281. [PubMed] [Google Scholar]
  36. Santiago-Schwarz F., Divaris N., Kay C., Carsons S. E. Mechanisms of tumor necrosis factor-granulocyte-macrophage colony-stimulating factor-induced dendritic cell development. Blood. 1993 Nov 15;82(10):3019–3028. [PubMed] [Google Scholar]
  37. Shimotohno K., Takahashi Y., Shimizu N., Gojobori T., Golde D. W., Chen I. S., Miwa M., Sugimura T. Complete nucleotide sequence of an infectious clone of human T-cell leukemia virus type II: an open reading frame for the protease gene. Proc Natl Acad Sci U S A. 1985 May;82(10):3101–3105. doi: 10.1073/pnas.82.10.3101. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Spiegel H., Herbst H., Niedobitek G., Foss H. D., Stein H. Follicular dendritic cells are a major reservoir for human immunodeficiency virus type 1 in lymphoid tissues facilitating infection of CD4+ T-helper cells. Am J Pathol. 1992 Jan;140(1):15–22. [PMC free article] [PubMed] [Google Scholar]
  39. 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]
  40. Tachibana N., Okayama A., Ishizaki J., Yokota T., Shishime E., Murai K., Shioiri S., Tsuda K., Essex M., Mueller N. Suppression of tuberculin skin reaction in healthy HTLV-I carriers from Japan. Int J Cancer. 1988 Dec 15;42(6):829–831. doi: 10.1002/ijc.2910420605. [DOI] [PubMed] [Google Scholar]
  41. 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]
  42. Van Voorhis W. C., Valinsky J., Hoffman E., Luban J., Hair L. S., Steinman R. M. Relative efficacy of human monocytes and dendritic cells as accessory cells for T cell replication. J Exp Med. 1983 Jul 1;158(1):174–191. doi: 10.1084/jem.158.1.174. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Welles S. L., Tachibana N., Okayama A., Shioiri S., Ishihara S., Murai K., Mueller N. E. Decreased reactivity to PPD among HTLV-I carriers in relation to virus and hematologic status. Int J Cancer. 1994 Feb 1;56(3):337–340. doi: 10.1002/ijc.2910560307. [DOI] [PubMed] [Google Scholar]
  44. Zucker-Franklin D., Grusky G., Marcus A. Transformation of monocytes into "fat" cells. Lab Invest. 1978 May;38(5):620–628. [PubMed] [Google Scholar]
  45. Zucker-Franklin D., Pancake B. A., Friedman-Kien A. E. Cutaneous disease resembling mycosis fungoides in HIV-infected patients whose skin and blood cells also harbor proviral HTLV type I. AIDS Res Hum Retroviruses. 1994 Sep;10(9):1173–1177. doi: 10.1089/aid.1994.10.1173. [DOI] [PubMed] [Google Scholar]
  46. Zucker-Franklin D., Yang J. S., Grusky G. Characterization of glycoprotein IIb/IIIa-positive cells in human umbilical cord blood: their potential usefulness as megakaryocyte progenitors. Blood. 1992 Jan 15;79(2):347–355. [PubMed] [Google Scholar]

Articles from Clinical and Diagnostic Laboratory Immunology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES