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

Objective: To study the requirements for HIV transfer between dendritic cel ls (DC) and CD4 T cells, using an in vitro model, combined with flow cytome try. Methods: Immature DC and macrophages (MA) were generated from monocytes. Af ter infection, DC or MA were cultured alone or with purified CD4 T cells. I ntracellular HIV was measured, using (1) the monocyte (MO)-tropic AD8 HIV, endowed with enhanced green fluorescent protein (EGFP); and (2) intracellul ar staining of laboratory HIV strains and clones from primary isolates. Results: (1) Clone AD8-EGFP infected DC and MA with equal efficiency, but t he 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 m embrane, if the T cells were in contact with non-infected DC. (4) Go-cultur e 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 autol ogous CD4 T cells was directly demonstrated using flow cytometry. The trans fer proceeded in both directions, depended on cellular contact and was asso ciated 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. (C) 2000 Lip pincott Williams & Wilkins.