Expression of a broad array of negative costimulatory molecules and Blimp-1 in T cells following priming by HIV-1 pulsed dendritic cells

• Published in: Molecular medicine (Cambridge, Mass.) Vol. 17; no. 3-4; pp. 229 - 240
• Main Authors: Shankar, Esaki Muthu, Che, Karlhans Fru, Messmer, Davorka, Lifson, Jeffrey D, Larsson, Marie
• Format: Journal Article
• Language: English
• Published: England ScholarOne 01-03-2011
• Subjects: Antigens, CD - genetics; Antigens, CD - metabolism; Cells, Cultured; CTLA-4 Antigen; Dendritic Cells - immunology; Dendritic Cells - metabolism; Flow Cytometry; Forkhead Transcription Factors - genetics; Forkhead Transcription Factors - metabolism; Gene Expression; GPI-Linked Proteins - genetics; GPI-Linked Proteins - metabolism; Hepatitis A Virus Cellular Receptor 2; HIV-1 - immunology; Humans; Immunophenotyping; Interferon-gamma - metabolism; Interleukin-2 - metabolism; MEDICIN; MEDICINE; Membrane Proteins - genetics; Membrane Proteins - metabolism; Positive Regulatory Domain I-Binding Factor 1; Receptors, Immunologic - genetics; Receptors, Immunologic - metabolism; Repressor Proteins - genetics; Repressor Proteins - metabolism; Reverse Transcriptase Polymerase Chain Reaction; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 1076-1551; 1528-3658
• DOI: 10.2119/molmed.2010.00175

Accumulating evidence indicates that immune impairment in persistent viral infections could lead to T-cell exhaustion. To evaluate the potential contribution of induction of negative costimulatory molecules to impaired T-cell responses, we primed naïve T cells with mature monocyte-derived dendritic cells (MDDCs) pulsed with HIV-1 in vitro. We used quantitative real-time polymerase chain reaction and flow cytometry, respectively, to compare the gene and surface-protein expression profiles of naïve T cells primed with HIV-pulsed or mock-pulsed DCs. We detected elevated expressions of negative costimulatory molecules, including lymphocyte activation gene-3 (LAG-3), CD160, cytolytic T-lymphocyte antigen-4 (CTLA-4), T-cell immunoglobulin mucin-containing domain-3 (TIM-3), programmed death-1 (PD-1) and TRAIL (tumor necrosis-factor-related apoptosis-inducing ligand) in T cells primed by HIV-pulsed DCs. The PD-1(+) T-cell population also coexpressed TIM-3, LAG-3, and CTLA-4. Interestingly, we also found an increase in gene expression of the transcriptional repressors Blimp-1 (B-lymphocyte-induced maturation protein-1) and Foxp3 (forkhead transcription factor) in T-cells primed by HIV-pulsed DCs; Blimp-1 expression was directly proportional to the expression of the negative costimulatory molecules. Furthermore, levels of the effector cytokines interleukin-2, tumor necrosis factor-α and interferon-γ, and perforin and granzyme B were decreased in T-cell populations primed by HIV-pulsed DCs. In conclusion, in vitro priming of naïve T-cells with HIV-pulsed DC leads to expansion of T cells with coexpression of a broad array of negative costimulatory molecules and Blimp-1, with potential deleterious consequences for T-cell responses.