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

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Summary

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.
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Keywords: dendritic cell subsets; interferon-γ production; lymphoproliferation; recall antigens

Document Type: Research Article

Affiliations: 1: Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina del Instituto Politécnico Nacional 2: Department of Molecular Biomedicine, Centro de Investigación y de Estudios Avanzados (CINVESTAV), Mexico City, Mexico

Publication date: November 1, 2007

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