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

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 (T_CM) and effector (T_EM) 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 T_EM at later time-points in the culture, whereas cells that had completed fewer cycles of division were similar to T_CM. The 16⁺ mDC induced higher rates of proliferation on both T_CM and T_EM 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 T_CM effector capacity in terms of interferon-γ production was faster and more pronounced with 16⁺ mDC, whereas both DC had similar abilities with T_EM. In conclusion, these data might reveal new potentials in vaccination protocols with 16⁺ mDC aimed at inducing strong responses on central memory T cells.