PMID- 10753825
OWN - NLM
STAT- MEDLINE
DCOM- 20000505
LR  - 20220317
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 95
IP  - 8
DP  - 2000 Apr 15
TI  - Granulocyte-colony stimulating factor mobilizes T helper 2-inducing dendritic 
      cells.
PG  - 2484-90
AB  - Peripheral blood stem cells (PBSC) obtained from granulocyte-colony stimulating 
      factor (G-CSF)-mobilized donors are increasingly used for allogeneic 
      transplantation. Despite a 10-fold higher dose of transplanted T cells, acute 
      graft-versus-host disease (GVHD) does not develop in higher proportion in 
      recipients of PBSC than in recipients of marrow. T cells from G-CSF-treated 
      experimental animals preferentially produce IL-4 and IL-10, cytokines 
      characteristic of Th2 responses, which are associated with diminished 
      GVHD-inducing ability. We hypothesized that G-CSF-mobilized PBSC contain 
      antigen-presenting cells, which prime T-lymphocytes to produce Th2 cytokines. Two 
      distinct lineages of dendritic cells (DC) have been described in humans, DC1 and 
      DC2, according to their ability to induce naive T-cell differentiation to Th1 and 
      Th2 effector cells, respectively. We have used multicolor microfluorometry to 
      enumerate DC1 and DC2 in the peripheral blood of normal donors. G-CSF treatment 
      with 10 to 16 microg/kg per day for 5 days increased peripheral blood DC2 counts 
      from a median of 4.9 x 10(6)/L to 24.8 x 10(6)/L (P =.0009), whereas DC1 counts 
      did not change. Purified DC1, from either untreated or G-CSF treated donors, 
      induced the proliferation of allogeneic naive T cells, but fresh DC2 were poor 
      stimulators. Tumor necrosis factor-alpha (TNF-alpha)-activated DC1 induced 
      allogeneic naive T cells to produce IFN-gamma, which is typical of Th1 responses, 
      whereas TNF-alpha-activated DC2 induced allogeneic naive T cells to produce IL-4 
      and IL-10, which are typical of Th2 responses. PBSC transplants contained higher 
      doses of DC2 than marrow transplants (median, 2.4 x 10(6)/kg versus 0.5 x 
      10(6)/kg) (P =.006), whereas the dose of DC1 was comparable. Thus, it is 
      conceivable that transplantation of G-CSF-stimulated PBSC does not result in 
      overwhelming acute GVHD because the graft contains predominantly Th2-inducing DC. 
      Adoptive transfer of purified DC2 may be exploited to induce immune deviation 
      after transplantation of hematopoietic stem cells or organ allografts. (Blood. 
      2000;95:2484-2490)
FAU - Arpinati, M
AU  - Arpinati M
AD  - Division of Clinical Research, Fred Hutchinson Cancer Research Center, University 
      of Washington, Seattle, WA, USA.
FAU - Green, C L
AU  - Green CL
FAU - Heimfeld, S
AU  - Heimfeld S
FAU - Heuser, J E
AU  - Heuser JE
FAU - Anasetti, C
AU  - Anasetti C
LA  - eng
GR  - AI33484/AI/NIAID NIH HHS/United States
GR  - AI37678/AI/NIAID NIH HHS/United States
GR  - CA18029/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 143011-72-7 (Granulocyte Colony-Stimulating Factor)
SB  - IM
CIN - Blood. 2000 Apr 15;95(8):2482-3. PMID: 10753824
CIN - Blood. 2000 Oct 1;96(7):2635. PMID: 11183128
CIN - Blood. 2001 Jan 1;97(1):333. PMID: 11194828
MH  - Adoptive Transfer
MH  - *Antigen Presentation
MH  - Dendritic Cells/*immunology
MH  - Graft vs Host Disease/immunology/prevention & control
MH  - Granulocyte Colony-Stimulating Factor/*pharmacology
MH  - *Hematopoietic Stem Cell Mobilization
MH  - Hematopoietic Stem Cell Transplantation
MH  - Humans
MH  - Th2 Cells/*immunology
MH  - *Transplantation Immunology
MH  - Transplantation, Homologous
EDAT- 2001/02/07 11:00
MHDA- 2001/02/07 11:01
CRDT- 2001/02/07 11:00
PHST- 2001/02/07 11:00 [pubmed]
PHST- 2001/02/07 11:01 [medline]
PHST- 2001/02/07 11:00 [entrez]
AID - S0006-4971(20)64135-0 [pii]
PST - ppublish
SO  - Blood. 2000 Apr 15;95(8):2484-90.