PMID- 18620796
OWN - NLM
STAT- MEDLINE
DCOM- 20081203
LR  - 20081016
IS  - 0301-472X (Print)
IS  - 0301-472X (Linking)
VI  - 36
IP  - 10
DP  - 2008 Oct
TI  - Regulation of alloimmune responses by dendritic cell subsets.
PG  - 1309-17
LID - 10.1016/j.exphem.2008.04.021 [doi]
AB  - OBJECTIVE: Dendritic cells (DCs) are powerful mediators of immune responses. We 
      have demonstrated that the content of plasmacytoid (type 2) dendritic cells (DC2) 
      within allogeneic bone marrow grafts impacts survival and graft-vs-host disease 
      following transplantation. In order to better understand the effect of DC subsets 
      on regulation of immunity, we tested the effect of DC subsets on T cells in a 
      model of indirect antigen presentation to mimic presentation of host-type 
      alloantigen by donor-type DC. MATERIALS AND METHODS: Volunteers underwent 
      apheresis without cytokine priming, and DC1, DC2, naive, and memory T cells were 
      purified by immunomagnetic bead and fluorescein-activated cell sorting. Purified 
      DC1 and DC2 cells were cultured with third-party irradiated blood mononuclear 
      cells and either naive or memory homologous T cells in mixed lymphocyte 
      reactions. RESULTS: Myeloid (type 1) dendritic cells (DC1) induced significant 
      proliferation of homologous T cells and were more effective in priming naive 
      T-cell responses than memory T cells responding to alloantigen. DC2 cells induced 
      minimal T-cell proliferation regardless of the T-cell subset used as the 
      responding fraction. Secondary mixed lymphocyte reaction studies demonstrated 
      that DC2 primed T cells remained hyporesponsive even when challenged with a 
      third-party alloantigen. The immunostimulatory effect of DC1 required 
      DC-to-T-cell contact, and induced interleukin-12 secretion, while DC2 cells 
      induced interferon-gamma secretion. Polymerase chain reaction analysis of 
      DC2-primed T cells demonstrated a significant increase in Foxp3 expression, 
      supporting induction of a regulatory T-cell population. CONCLUSION: DC1 and DC2 
      cells induced divergent T-cell responses using homologous cells. Better 
      understanding of DC2-mediated T-cell suppression may yield strategies that 
      overcome tumor-specific immune tolerance and regulate graft-vs-host disease.
FAU - Lonial, Sagar
AU  - Lonial S
AD  - Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA 30322, 
      USA. sloni01@emory.edu
FAU - Torre, Claire
AU  - Torre C
FAU - David, Ebenezer
AU  - David E
FAU - Harris, Wayne
AU  - Harris W
FAU - Arellano, Martha
AU  - Arellano M
FAU - Waller, Edmund K
AU  - Waller EK
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080711
PL  - Netherlands
TA  - Exp Hematol
JT  - Experimental hematology
JID - 0402313
RN  - 0 (Antigens, CD)
RN  - 0 (Cytokines)
RN  - 0 (FOXP3 protein, human)
RN  - 0 (Forkhead Transcription Factors)
SB  - IM
MH  - Antigens, CD/analysis/immunology
MH  - Cell Division
MH  - Cell Separation
MH  - Cytokines/analysis/immunology
MH  - Dendritic Cells/cytology/drug effects/*immunology
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Flow Cytometry
MH  - Forkhead Transcription Factors/analysis/genetics
MH  - Humans
MH  - Immunologic Memory
MH  - Lymphocyte Activation
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - T-Lymphocytes/cytology/immunology
EDAT- 2008/07/16 09:00
MHDA- 2008/12/17 09:00
CRDT- 2008/07/16 09:00
PHST- 2006/12/18 00:00 [received]
PHST- 2008/04/01 00:00 [revised]
PHST- 2008/04/30 00:00 [accepted]
PHST- 2008/07/16 09:00 [pubmed]
PHST- 2008/12/17 09:00 [medline]
PHST- 2008/07/16 09:00 [entrez]
AID - S0301-472X(08)00210-5 [pii]
AID - 10.1016/j.exphem.2008.04.021 [doi]
PST - ppublish
SO  - Exp Hematol. 2008 Oct;36(10):1309-17. doi: 10.1016/j.exphem.2008.04.021. Epub 
      2008 Jul 11.