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Decreased CD4 and wide-ranging expression of other immune receptors after HIV-envelope-mediated formation of syncytia in vitro

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Abstract

In human HIV infection, multinucleated cells (syncytia) are formed by fusion of HIV-infected cells with CD4+ cells. In order to examine possible functional implications of syncytia formation for the immune response, the expression of important surface molecules by T-cell syncytia and surrounding cells that remain unfused (bystander cells) was analyzed in cocultures of HIV-Env- and CD4-expressing E6 Jurkat T cells. Fusion partners were differentially labeled with lipophilic probes, and syncytia and bystander cells were identified by flow cytometry. The cellular phenotype and response to activation stimulus after fusion were analyzed with antibodies coupled to third-party fluorochromes. Cocultured unfused E6 cells showed a marked decrease in CD4 expression, suggesting the selective recruitment of cells strongly expressing CD4 into syncytia. However, the incorporated CD4 was not detected in the syncytia, whereas the range of expression of CD28, ICAM-1, CXCR4 and CD3 was wider than that of unfused cells. Limited expression of CD4 in the bystander unfused population, as well as in the newly formed syncytia, would result in limitation of further viral entry and a failure to identify these cells, and it could partially contribute to functional impairment and a decrease in the number of CD4+ T cells in AIDS. Most of the syncytia were viable and expressed CD25 and IL-2 in response to activation by phorbol myristate acetate (PMA) and ionomicyn. Thus, syncytia populations harboring widely heterogeneous levels of receptors would constitute a potential source of anomalous immune function.

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Acknowledgments

Jurkat-HXBc2(4) and Jurkat-522F/Y cells were obtained from Dr. Joseph Sodroski, and Jurkat Clone E6-1 cells from ATCC (Dr. Arthur Weiss), through the AIDS Research and Reference Reagent Program, Division of AIDS, NIAID, NIH. This work was supported by Consejo Nacional de Ciencia y Tecnología of México (CONACYT), grant 61425 and the Dirección General de Asuntos del Personal Académico, Universidad Nacional Autónoma de México, grant IN229307. Evelyn Rivera-Toledo and Nayali López-Balderas were recipients of a fellowship from CONACYT. We appreciate the expert technical assistance of Carlos Castellanos with cell sorting.

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The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Immunology, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Apartado Postal 70228, Ciudad Universitaria, Distrito Federal, C.P. 04510, Mexico

    Evelyn Rivera-Toledo, Nayali López-Balderas, Leonor Huerta, Edmundo Lamoyi & Carlos Larralde

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  1. Evelyn Rivera-Toledo
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  2. Nayali López-Balderas
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  3. Leonor Huerta
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  4. Edmundo Lamoyi
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  5. Carlos Larralde
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Correspondence to Leonor Huerta.

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E. Rivera-Toledo and N. López-Balderas contributed equally to this work and are listed as co-first authors.

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Rivera-Toledo, E., López-Balderas, N., Huerta, L. et al. Decreased CD4 and wide-ranging expression of other immune receptors after HIV-envelope-mediated formation of syncytia in vitro. Arch Virol 155, 1205–1216 (2010). https://doi.org/10.1007/s00705-010-0704-2

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  • DOI: https://doi.org/10.1007/s00705-010-0704-2

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