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Blood, 12 November 2009, Vol. 114, No. 20, pp. 4422-4431.
Prepublished online as a Blood First Edition Paper on September 17, 2009; DOI 10.1182/blood-2009-06-227256.
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IMMUNOBIOLOGY
CD56+ human blood dendritic cells effectively promote TH1-type   T-cell responses
Georg Gruenbacher1,2,
Hubert Gander1,2,
Andrea Rahm1,2,
Walter Nussbaumer3,
Nikolaus Romani1,2, and
Martin Thurnher1,2
1 Cell Therapy Unit, Departments of Urology and Dermatology and Venereology, Innsbruck Medical University, Innsbruck;
2 K1 Center Oncotyrol, Innsbruck; and
3 Central Institute for Blood Transfusion, Innsbruck, Austria
CD56+ human dendritic cells (DCs) have recently been shown to differentiate from monocytes in response to GM-CSF and type 1 interferon in vitro. We show here that CD56+ cells freshly isolated from human peripheral blood contain a substantial subset of CD14+CD86+HLA-DR+ cells, which have the appearance of intermediate-sized lymphocytes but spontaneously differentiate into enlarged DC-like cells with substantially increased HLA-DR and CD86 expression or into fully mature CD83+ DCs in response to appropriate cytokines. Stimulation of CD56+ cells containing both DCs and abundant   T cells with zoledronate and interleukin-2 (IL-2) resulted in the rapid expansion of T cells as well as in IFN-, TNF- , and IL-1β but not in IL-4, IL-10, or IL-17 production. IFN-, TNF-, and IL-1β production were almost completely abolished by depleting CD14+ cells from the CD56+ subset before stimulation. Likewise, depletion of CD14+ cells dramatically impaired T-cell expansion. IFN- production could also be blocked by neutralizing the effects of endogenous IL-1β and TNF-. Conversely, addition of recombinant IL-1β, TNF-, or both further enhanced IFN- production and strongly up-regulated IL-6 production. Our data indicate that CD56+ DCs from human blood are capable of stimulating CD56+ T cells, which may be harnessed for immunotherapy.
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