Abstract
Dendritic cells isolated from thymus and tonsil were tested for susceptibility to HIV-1 strains that are tropic for macrophages or for T cell lines. DCs were purified by cell sorting and before infection expressed high levels of CD4 and HLA-DR and lacked markers for T, B, NK cells, or macrophages. Viral entry and reverse transcription was found after pulsing with strains of HIV-1 that could infect macrophages. During the first 36 h the PCR signals for gag sequences increased in DCs and macrophages. In contrast little if any viral DNA was found after pulsing macrophages or DCs with HIV-1 that was able to infect T cell lines. DCs pulsed with HIV-1 were able to transmit infection to responding T cells during an allogeneic or superantigen response. Selection for virus able to infect lymphoid DCs and other DCs expressing CD4 and its transfer to T cells during subsequent immune responses may provide a mechanism for the observed predominance of macrophage-tropic HIV-1 after in vivo transmission.
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Selected References
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- Ardavin C., Wu L., Li C. L., Shortman K. Thymic dendritic cells and T cells develop simultaneously in the thymus from a common precursor population. Nature. 1993 Apr 22;362(6422):761–763. doi: 10.1038/362761a0. [DOI] [PubMed] [Google Scholar]
- 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]
- Cameron P. U., Lowe M. G., Crowe S. M., O'Doherty U., Pope M., Gezelter S., Steinman R. M. Susceptibility of dendritic cells to HIV-1 infection in vitro. J Leukoc Biol. 1994 Sep;56(3):257–265. doi: 10.1002/jlb.56.3.257. [DOI] [PubMed] [Google Scholar]
- Cameron P. U., Pope M., Gezelter S., Steinman R. M. Infection and apoptotic cell death of CD4+ T cells during an immune response to HIV-1-pulsed dendritic cells. AIDS Res Hum Retroviruses. 1994 Jan;10(1):61–71. doi: 10.1089/aid.1994.10.61. [DOI] [PubMed] [Google Scholar]
- Chehimi J., Prakash K., Shanmugam V., Collman R., Jackson S. J., Bandyopadhyay S., Starr S. E. CD4-independent infection of human peripheral blood dendritic cells with isolates of human immunodeficiency virus type 1. J Gen Virol. 1993 Jul;74(Pt 7):1277–1285. doi: 10.1099/0022-1317-74-7-1277. [DOI] [PubMed] [Google Scholar]
- Clerici M., Landay A. L., Kessler H. A., Zajac R. A., Boswell R. N., Muluk S. C., Shearer G. M. Multiple patterns of alloantigen presenting/stimulating cell dysfunction in patients with AIDS. J Immunol. 1991 Apr 1;146(7):2207–2213. [PubMed] [Google Scholar]
- 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]
- Hart D. N., McKenzie J. L. Isolation and characterization of human tonsil dendritic cells. J Exp Med. 1988 Jul 1;168(1):157–170. doi: 10.1084/jem.168.1.157. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hart D. N., Starling G. C., Calder V. L., Fernando N. S. B7/BB-1 is a leucocyte differentiation antigen on human dendritic cells induced by activation. Immunology. 1993 Aug;79(4):616–620. [PMC free article] [PubMed] [Google Scholar]
- Knight S. C., Farrant J., Bryant A., Edwards A. J., Burman S., Lever A., Clarke J., Webster A. D. Non-adherent, low-density cells from human peripheral blood contain dendritic cells and monocytes, both with veiled morphology. Immunology. 1986 Apr;57(4):595–603. [PMC free article] [PubMed] [Google Scholar]
- 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]
- 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]
- Miedema F., Petit A. J., Terpstra F. G., Schattenkerk J. K., de Wolf F., Al B. J., Roos M., Lange J. M., Danner S. A., Goudsmit J. Immunological abnormalities in human immunodeficiency virus (HIV)-infected asymptomatic homosexual men. HIV affects the immune system before CD4+ T helper cell depletion occurs. J Clin Invest. 1988 Dec;82(6):1908–1914. doi: 10.1172/JCI113809. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- 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]
- 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]
- Petit A. J., Tersmette M., Terpstra F. G., de Goede R. E., van Lier R. A., Miedema F. Decreased accessory cell function by human monocytic cells after infection with HIV. J Immunol. 1988 Mar 1;140(5):1485–1489. [PubMed] [Google Scholar]
- Pinchuk L. M., Polacino P. S., Agy M. B., Klaus S. J., Clark E. A. The role of CD40 and CD80 accessory cell molecules in dendritic cell-dependent HIV-1 infection. Immunity. 1994 Jul;1(4):317–325. doi: 10.1016/1074-7613(94)90083-3. [DOI] [PubMed] [Google Scholar]
- Sotzik F., Rosenberg Y., Boyd A. W., Honeyman M., Metcalf D., Scollay R., Wu L., Shortman K. Assessment of CD4 expression by early T precursor cells and by dendritic cells in the human thymus. J Immunol. 1994 Apr 1;152(7):3370–3377. [PubMed] [Google Scholar]
- Stanley S. K., McCune J. M., Kaneshima H., Justement J. S., Sullivan M., Boone E., Baseler M., Adelsberger J., Bonyhadi M., Orenstein J. Human immunodeficiency virus infection of the human thymus and disruption of the thymic microenvironment in the SCID-hu mouse. J Exp Med. 1993 Oct 1;178(4):1151–1163. doi: 10.1084/jem.178.4.1151. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- 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]
- Valentin H., Nugeyre M. T., Vuillier F., Boumsell L., Schmid M., Barré-Sinoussi F., Pereira R. A. Two subpopulations of human triple-negative thymic cells are susceptible to infection by human immunodeficiency virus type 1 in vitro. J Virol. 1994 May;68(5):3041–3050. doi: 10.1128/jvi.68.5.3041-3050.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- 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]
- Young J. W., Steinman R. M. Accessory cell requirements for the mixed-leukocyte reaction and polyclonal mitogens, as studied with a new technique for enriching blood dendritic cells. Cell Immunol. 1988 Jan;111(1):167–182. doi: 10.1016/0008-8749(88)90061-5. [DOI] [PubMed] [Google Scholar]
- Zhu T., Mo H., Wang N., Nam D. S., Cao Y., Koup R. A., Ho D. D. Genotypic and phenotypic characterization of HIV-1 patients with primary infection. Science. 1993 Aug 27;261(5125):1179–1181. doi: 10.1126/science.8356453. [DOI] [PubMed] [Google Scholar]