Cytokine and chemokine expression profiles of maturing dendritic cells using multiprotein platform arrays.
Understanding the whole process of dendritic cell (DC) activation might help in the development of more efficient immunotherapeutic strategies for tumor patients. Part of this process is cytokine secretion, which has important effects on innate and adaptive immune response. Here, we cultured circulating monocytes for five days with interleukin-4 and GM-CSF followed by two-day culture with or without CD40 ligand and LPS to create a mature DC (mDC) and an immature DC (iDC) phenotype, respectively, characterized by differential expression of co-stimulatory molecules (CD80, CD83). We then compared the cytokine expression profile of the mDC and iDC using two protein platform arrays. Twelve supernatants from mDC paired with 12 from iDC were compared. The mDC protein expression profile showed significant increases in 16 out of 34 factors tested, including TNFalpha, IL-10, IL-12, IFNgamma, MIP1alpha, MIP1beta, IL-8, MDC, RANTES, and IL-6, which play a crucial role in the regulation of the innate immune response as well as the recruitment and activation of adaptive immune effectors. Interestingly, some of the cytokines expressed during maturation were also found in the gene expression profile identified in tumor metastases following IL-2 therapy using cDNA arrays. This finding suggests a possible role for resident DC maturation as a mediator of systemic IL-2 effects. Most important, the array of cytokines secreted during DC maturation may be considered an important component during adoptive transfer. Further characterization of the kinetics and persistence of their secretion should be undertaken in the future.
Nagorsen
Dirk
D
Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, MD 20892-1502, USA.
Marincola
Francesco M
FM
Panelli
Monica C
MC
D015703:Antigens, CD; D018122:B7-1 Antigen / Q000378:metabolism; D023201:CD40 Ligand / Q000494:pharmacology; D002478:Cells, Cultured; D054422:Chemokine CCL22; D018946:Chemokine CCL5 / Q000378:metabolism; D018925:Chemokines / Q000378:metabolism*; D019742:Chemokines, CC / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D003713:Dendritic Cells / Q000187:drug effects / Q000502:physiology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006801:Humans; D007136:Immunoglobulins / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000378:metabolism; D040081:Protein Array Analysis / Q000379:methods*; D000097802:CD83 Antigen
D015703:Antigens, CD; D018122:B7-1 Antigen; D023201:CD40 Ligand; D054422:Chemokine CCL22; D018946:Chemokine CCL5; D018925:Chemokines; D019742:Chemokines, CC; D016207:Cytokines; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D007136:Immunoglobulins; D007376:Interleukin-2; D015847:Interleukin-4; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D000097802:CD83 Antigen; C515482:CCL22 protein, human