PMID- 11929777
OWN - NLM
STAT- MEDLINE
DCOM- 20020617
LR  - 20211008
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 99
IP  - 8
DP  - 2002 Apr 15
TI  - Increased dendritic cell number and function following continuous in vivo 
      infusion of granulocyte macrophage-colony-stimulating factor and interleukin-4.
PG  - 2869-79
AB  - Dendritic cells (DCs) are rare antigen-presenting cells that play a central role 
      in stimulating immune responses. The combination of recombinant granulocyte 
      macrophage-colony-stimulating factor (rGM-CSF) and recombinant interleukin-4 
      (rIL-4) provides an important stimulus for generating DCs from murine bone marrow 
      precursors in vitro. Using miniature osmotic pumps, we now demonstrate that 
      continuous infusion of these cytokines for 7 days had a similar effect in vivo, 
      increasing the number and function of splenic DCs. Administration of 
      rGM-CSF/rIL-4 (10 microg/d each) increased the concentration of CD11(+) DCs by 
      2.7-fold and the absolute number of splenic DCs by an average of 5.7-fold. DC 
      number also increased in peripheral blood and lymph nodes. The resultant DCs 
      exhibited a different phenotype and function than those in control mice or mice 
      treated with rGM-CSF alone. rGM-CSF/IL-4 increased both the myeloid 
      (CD11c(+)/CD11b(+)) and the lymphoid (CD11c(+)/CD8alpha(+)) subpopulations, 
      whereas rGM-CSF increased only myeloid DCs. DCs were highly concentrated in the 
      T-cell areas of white pulp after rGM-CSF/IL-4 administration, whereas they were 
      diffusely distributed throughout white pulp, marginal zones, and red pulp in mice 
      treated with rGM-CSF alone. rGM-CSF/rIL-4 also significantly increased the 
      expression of major histocompatibility complex (MHC) class I and MHC class II on 
      CD11c(+) cells and increased their capacity to take up antigens by 
      macropinocytosis and receptor-mediated endocytosis. Splenic DCs generated in 
      response to rGM-CSF/rIL-4 were functionally immature in terms of allostimulatory 
      activity, but this activity increased after short-term in vitro culture. Systemic 
      treatment with rGM-CSF/rIL-4 enhanced the response to an adenoviral-based vaccine 
      and led to antigen-specific retardation in the growth of established tumor. We 
      conclude that systemic therapy with the combination of rGM-CSF/rIL-4 provides a 
      new approach for generating DCs in vivo.
FAU - Basak, Saroj K
AU  - Basak SK
AD  - Division of Pulmonary and Critical Care, Department of Medicine, UCLA School of 
      Medicine, Los Angeles 90095-1690, USA. sbasak@mednet.ucla.edu
FAU - Harui, Airi
AU  - Harui A
FAU - Stolina, Marina
AU  - Stolina M
FAU - Sharma, Sherven
AU  - Sharma S
FAU - Mitani, Kohnosuke
AU  - Mitani K
FAU - Dubinett, Steven M
AU  - Dubinett SM
FAU - Roth, Michael D
AU  - Roth MD
LA  - eng
GR  - AI28697/AI/NIAID NIH HHS/United States
GR  - CA16042/CA/NCI NIH HHS/United States
GR  - CA85686/CA/NCI NIH HHS/United States
GR  - IP50 CA90388/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Cancer Vaccines)
RN  - 0 (Histocompatibility Antigens)
RN  - 207137-56-2 (Interleukin-4)
RN  - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor)
SB  - IM
MH  - Animals
MH  - Cancer Vaccines
MH  - Cell Count
MH  - Cell Differentiation/drug effects
MH  - Cell Division/drug effects
MH  - Cell Lineage/drug effects
MH  - Dendritic Cells/cytology/*drug effects/immunology
MH  - Drug Interactions
MH  - Endocytosis/drug effects
MH  - Granulocyte-Macrophage Colony-Stimulating Factor/administration & 
      dosage/*pharmacology
MH  - Histocompatibility Antigens/drug effects/metabolism
MH  - Immunotherapy
MH  - Infusions, Parenteral
MH  - Interleukin-4/administration & dosage/*pharmacology
MH  - Lymph Nodes/cytology/drug effects
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - Neoplasms, Experimental/drug therapy/therapy
MH  - Spleen/cytology/drug effects
MH  - Treatment Outcome
EDAT- 2002/04/04 10:00
MHDA- 2002/06/18 10:01
CRDT- 2002/04/04 10:00
PHST- 2002/04/04 10:00 [pubmed]
PHST- 2002/06/18 10:01 [medline]
PHST- 2002/04/04 10:00 [entrez]
AID - S0006-4971(20)37974-X [pii]
AID - 10.1182/blood.v99.8.2869 [doi]
PST - ppublish
SO  - Blood. 2002 Apr 15;99(8):2869-79. doi: 10.1182/blood.v99.8.2869.