Modeling HIV transfer between dendritic cells and T cells: importance of HIV phenotype, dendritic cell-T cell contact and T-cell activation

AIDS. 2000 Oct 20;14(15):2299-311. doi: 10.1097/00002030-200010200-00011.

Abstract

Objective: To study the requirements for HIV transfer between dendritic cells (DC) and CD4 T cells, using an in vitro model, combined with flow cytometry.

Methods: Immature DC and macrophages (MA) were generated from monocytes. After infection, DC or MA were cultured alone or with purified CD4 T cells. Intracellular HIV was measured, using (1) the monocyte (MO)-tropic AD8 HIV, endowed with enhanced green fluorescent protein (EGFP); and (2) intracellular staining of laboratory HIV strains and clones from primary isolates.

Results: (1) Clone AD8-EGFP infected DC and MA with equal efficiency, but the virus was preferentially transferred from DC to autologous T cells. (2) DC were more productively infected with R5/NSI, as compared to X4/SI, HIV, but both HIV phenotypes were easily transmitted to autologous T4 cells. (3) HIV-infected DC transferred the virus to T cells across a semi-permeable membrane, if the T cells were in contact with non-infected DC. (4) Co-culture of T cells with autologous non-infected DC induced T-cell activation. HIV-infected DC selectively increased HLA-DR on T cells and HLA-DR (+) T cells were preferential targets for HIV transfer. (5) Resting Ba-L-infected CD4 T cells were able to transmit the virus 'inversely' to co-cultured DC.

Conclusion: HIV transfer between monocyte-derived dendritic cells and autologous CD4 T cells was directly demonstrated using flow cytometry. The transfer proceeded in both directions, depended on cellular contact and was associated with partial T-cell activation. This model, representing relevant in vivo targets of HIV, is useful to further investigate interactions between HIV, DC and T cells, without the need for primary ex vivo DC.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / virology
  • Cell Communication
  • Cells, Cultured
  • Dendritic Cells / cytology
  • Dendritic Cells / virology*
  • Genetic Variation
  • HIV / genetics
  • HIV / growth & development*
  • HLA-DR Antigens
  • Humans
  • Lymphocyte Activation
  • Macrophages / cytology
  • Macrophages / virology
  • Models, Biological
  • Monocytes / cytology
  • Monocytes / virology
  • T-Lymphocytes / cytology
  • T-Lymphocytes / virology*

Substances

  • HLA-DR Antigens