Anti-CD25 antibodies affect cytokine synthesis pattern of human dendritic cells and decrease their ability to prime allogeneic CD4 super(+) T cells

• Published in: Journal of leukocyte biology Vol. 84; no. 2; pp. 460 - 467
• Main Authors: Mnasria, K, Lagaraine, C, Velge-Roussel, F, Oueslati, R, Lebranchu, Y, Baron, C
• Format: Journal Article
• Language: English
• Published: 01.08.2008
• ISSN: 0741-5400
• DOI: 10.1189/jlb.1007712

Anti-CD25 monoclonal antibodies are widely used in clinical transplantation to prevent acute allograft rejection. Although their effects on T lymphocytes have been extensively studied, their impact on human dendritic cells (DC) has never been reported. Furthermore, the role of the IL-2 in DC functions has not yet been fully elucidated. In this study, we confirm that the stimulation of human monocyte-derived DC with LPS strongly induced the expression of CD25 and that LPS-matured DC also expressed the beta and gamma chain of the IL-2R. We also showed that adding anti-CD25 monoclonal antibodies to LPS induced a decrease in IL-12, IL-1, TNF- alpha , IL-6, and IFN- gamma production and an increase in IL-10 synthesis by DC compared with stimulation with LPS alone. Furthermore, we showed that these modifications diminished the T helper priming ability of DC and polarized the alloimmune response toward TH2. In contrast, humanized anti-CD25 monoclonal antibodies did not affect the up-regulation of CD86, CD80, CD83, HLADR, or CD40 induced upon LPS stimulation. Taken together, this study discloses some previously unrecognized effects of anti-CD25 monoclonal antibodies on DC that may contribute to their clinical efficacy. In addition, this study also shed some light on the role of the IL-2 in human DC activation.