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Blood, 15 October 2006, Vol. 108, No. 8, pp. 2655-2661.
Prepublished online as a Blood First Edition Paper on June 8, 2006; DOI 10.1182/blood-2006-03-011353.
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IMMUNOBIOLOGY
Expansion of FOXP3high regulatory T cells by human dendritic cells (DCs) in vitro and after injection of cytokine-matured DCs in myeloma patients
Devi K. Banerjee,
Madhav V. Dhodapkar,
Elyana Matayeva,
Ralph M. Steinman, and
Kavita M. Dhodapkar
From the Laboratory of Cellular Physiology and Immunology, Laboratory of Tumor Immunology and Immunotherapy, and the Chris Browne Center for Immunology Research, The Rockefeller University, New York, NY.
CD4+CD25+FOXP3+ regulatory T cells (Treg's) play an important role in the maintenance of immune tolerance. The mechanisms controlling the induction and maintenance of Treg's in humans need to be defined. We find that human myeloid dendritic cells (DCs) are superior to other antigen presenting cells for the maintenance of FOXP3+ Treg's in culture. Coculture of DCs with autologous T cells leads to an increase in both the number of Treg's, as well as the expression of FOXP3 protein per cell both in healthy donors and myeloma patients. DC-mediated expansion of FOXP3high Treg's is enhanced by endogenous but not exogenous interleukin-2 (IL-2), and DC-T-cell contact, including the CD80/CD86 membrane costimulatory molecules. DCs also stimulate the formation of Treg's from CD25- T cells. The efficacy of induction of Treg's by DCs depends on the nature of the DC maturation stimulus, with inflammatory cytokine-treated DCs (Cyt-DCs) being the most effective Treg inducers. DC-induced Treg's from both healthy donors and patients with myeloma are functional and effectively suppress T-cell responses. A single injection of cytokine-matured DCs led to rapid enhancement of FOXP3+ Treg's in vivo in 3 of 3 myeloma patients. These data reveal a role for DCs in increasing the number of functional FOXP3high Treg's in humans.
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