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Published online before print May 8, 2008

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(Journal of Leukocyte Biology. 2008;84:460-467.)
© 2008 by Society for Leukocyte Biology

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

K. Mnasria^*,1,2, C. Lagaraine^*,1, F. Velge-Roussel^*,, R. Oueslati, Y. Lebranchu^*, and C. Baron^*,,3

^* JE 2448, "Cellules Dendritiques et Greffes," Faculté de Medicine, Université François Rabelais, Tours, France;
UFR des Sciences Pharmaceutiques, Tours, France;
UR Immuno-Microbiologie Environnementale et Cancérogenèse, Faculté des Sciences de Bizerte, and Banque de Tissus, Hôpital Militaire de Tunis, Tunis, Tunisia; and
Department of Immunology and Nephrology, Bretonneau Hospital, Tours, France

³ Correspondence: Faculté de Médecine, Université François Rabelais, Equipe JE 2448 "Cellules Dendritiques et Greffe," 10 Bd Tonnelle, 37032 Tours Cedex, France. E-mail: baron{at}med.univ-tours.fr

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 β and 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-, IL-6, and IFN- 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.

Key Words: interleukin-2 • DC maturation • DC activation