Differential CD4⁺ T-cell memory responses induced by two subsets of human monocyte-derived dendritic cells

• Published in: Immunology Vol. 122; no. 3; pp. 381 - 393
• Main Authors: Bajaña, Sandra, Herrera-González, Norma, Narváez, Juana, Torres-Aguilar, Honorio, Rivas-Carvalho, Amaranta, Aguilar, Sergio R, Sánchez-Torres, Carmen
• Format: Journal Article
• Language: English
• Published: Oxford, UK Oxford, UK : Blackwell Publishing Ltd 01.11.2007; Blackwell Publishing Ltd; Blackwell Science Inc
• Subjects: Antigen Presentation - immunology; CD4-Positive T-Lymphocytes - immunology; Cell Proliferation; Cells, Cultured; dendritic cell subsets; Dendritic Cells - immunology; Dose-Response Relationship, Immunologic; Humans; Immunologic Memory; Immunophenotyping; Interferon-gamma - biosynthesis; interferon-γ production; Lymphocyte Activation - immunology; lymphoproliferation; Original; recall antigens; Tetanus Toxoid - immunology; Tuberculin - immunology
• ISSN: 0019-2805; 1365-2567
• DOI: 10.1111/j.1365-2567.2007.02650.x

Dendritic cells (DC) are powerful inducers of primary T-cell responses, but their role in secondary responses has not been extensively analysed. Here, we address the role of two DC subsets derived from human CD16⁺ (16⁺ mDC) or CD16⁻ (16⁻ mDC) monocytes on the reactivation of memory responses. CD4⁺ CD45RA⁻ memory T cells were obtained from adult blood donors, and central (TCM) and effector (TEM) memory T cells were isolated by fluorescence-activated cell sorting with anti-CCR7 antibodies. The 16⁺ mDC and 16⁻ mDC were cocultured with autologous lymphocytes, either unpulsed or loaded with purified protein derivatives of Mycobacterium tuberculosis (PPD) or tetanus toxoid (TT), and were analysed for up to 8 days. Over a range of doses, 16⁺ mDC drove stronger T-cell proliferative responses against both antigens. Overall, antigen-specific memory cells tended to acquire a phenotype of TEM at later time-points in the culture, whereas cells that had completed fewer cycles of division were similar to TCM. The 16⁺ mDC induced higher rates of proliferation on both TCM and TEM lymphocytes than 16⁻ mDC. This phenomenon was not related to the ability of both DC to induce CD25 expression on T cells, to lower secretion of interleukin-2, or to raise production of interleukin-10 during T-cell/16⁻ mDC cocultures. The induction of TCM effector capacity in terms of interferon-γ production was faster and more pronounced with 16⁺ mDC, whereas both DC had similar abilities with TEM. In conclusion, these data might reveal new potentials in vaccination protocols with 16⁺ mDC aimed at inducing strong responses on central memory T cells.