Efficient In Vitro Expansion of Human Immunodeficiency Virus (HIV)-Specific T-Cell Responses bygagmRNA-Electroporated Dendritic Cells from Treated and Untreated HIV Type 1-Infected Individuals

• DOI: 10.1128/jvi.02080-07
• Publication Date: 2008-01-31T01:46:47Z
• Authors: Ellen R. Van Gulck; Guido Vanham; Leo Heyndrickx; Sandra Coppens; Katleen Vereecken; Derek Atkinson; Eric Florence; Ilse Kint; Zwi Nisan Berneman; Viggo Van Tendeloo
• Keywords: 0301 basic medicine; 570; Perforin; T-cells; T-Lymphocytes; 610; HIV Infections; Dendritic Cells; Dendritic cells; Gag mRNA; gag Gene Products, Human Immunodeficiency Virus; 3. Good health; Interferon-gamma; 03 medical and health sciences; Electroporation; Virology; HIV-1; Humans; Interleukin-2; RNA, Viral; Immunotherapy; RNA, Messenger; Immune response; Epitope Mapping

Developing an immunotherapy to keep human immunodeficiency virus type 1 (HIV-1) replication suppressed while discontinuing highly active antiretroviral therapy (HAART) is important challenge. In the present work, we evaluated in vitro whether dendritic cells (DC) electroporated with gag mRNA can induce HIV-specific responses T from chronically infected subjects. Monocyte-derived DC, therapy-naïve and HAART-treated HIV-1-seropositive subjects, that were consensus codon-optimized HxB2 efficiently expanded cells, secreting gamma interferon (IFN-gamma) interleukin 2 (IL-2), as well other cytokines perforin, upon restimulation a pool of overlapping Gag peptides. The functional expansion levels after week stimulation comparable treatment-naïve patients involved both CD4(+) CD8(+) evidence bifunctionality cells. Epitope mapping p24 showed stimulated had broadened response toward previously nondescribed epitopes. autologous proviral equally Regulatory did not prevent induction effector this system, whereas blocking PD-L1 slightly increased T-cell responses. This paper shows loaded or mRNA, expand vitro.