PMID- 11735338
OWN - NLM
STAT- MEDLINE
DCOM- 20020206
LR  - 20121115
IS  - 1525-0016 (Print)
IS  - 1525-0016 (Linking)
VI  - 4
IP  - 6
DP  - 2001 Dec
TI  - Viral IL-10 gene transfer inhibits DTH responses to soluble antigens: evidence 
      for involvement of genetically modified dendritic cells and macrophages.
PG  - 543-50
AB  - Expression of the viral interleukin-10 (vIL-10) gene within one joint of an 
      animal with polyarticular, inflammatory arthritis suppresses disease in both 
      treated and untreated joints (the "contralateral effect"). We used a mouse 
      delayed-type hypersensitivity (DTH) model to investigate this phenomenon. 
      Adenoviral delivery of the vIL-10 gene suppressed DTH reactions in injected and 
      contralateral paws. T lymphocytes recovered from immunized mice injected with the 
      adenoviral vector (ad-vIL-10) were unable to transfer the DTH response, but were 
      not inhibitory. Peritoneal exudate cells recovered from mice injected 
      intraperitoneally with ad-vIL-10 inhibited DTH reactions in recipient mice, but 
      only when the donor mice had been sensitized to the antigen used to incite the 
      DTH response. Dendritic cells (DCs) recovered from the draining lymph nodes of 
      mice injected with ad-vIL-10 behaved similarly. Bone-marrow-derived DCs cultured 
      ex vivo with ad-vIL-10 or recombinant mouse IL-10 also suppressed DTH reactions 
      by adoptive transfer when pulsed with the inciting antigen. Collectively, these 
      data suggest a mechanism for the contralateral effect in which genetically 
      modified macrophages and DCs present antigen in the context of high, local 
      concentrations of vIL-10, thereby generating unresponsive T lymphocytes. These 
      findings suggest new ways in which to treat immune-driven diseases by gene and 
      cell therapy.
FAU - Whalen, J D
AU  - Whalen JD
AD  - Department of Molecular Genetics and Biochemistry, University of Pittsburgh, 
      Pittsburgh, Pennsylvania 15312, USA.
FAU - Thomson, A W
AU  - Thomson AW
FAU - Lu, L
AU  - Lu L
FAU - Robbins, P D
AU  - Robbins PD
FAU - Evans, C H
AU  - Evans CH
LA  - eng
GR  - P01 DK 44935/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Mol Ther
JT  - Molecular therapy : the journal of the American Society of Gene Therapy
JID - 100890581
RN  - 130068-27-8 (Interleukin-10)
SB  - IM
MH  - Adenoviridae/*physiology
MH  - Adoptive Transfer
MH  - Animals
MH  - Arthritis, Experimental/immunology/pathology/*prevention & control
MH  - Autoimmunity
MH  - Dendritic Cells/*immunology
MH  - Gene Transfer Techniques
MH  - Genetic Therapy/methods
MH  - Genetic Vectors/therapeutic use
MH  - Hypersensitivity, Delayed/immunology/pathology/*prevention & control
MH  - Interleukin-10/*genetics
MH  - Lymph Nodes/cytology
MH  - Lymphocyte Activation
MH  - Macrophages/*immunology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - T-Lymphocytes/immunology
EDAT- 2001/12/12 10:00
MHDA- 2002/02/07 10:01
CRDT- 2001/12/12 10:00
PHST- 2001/12/12 10:00 [pubmed]
PHST- 2002/02/07 10:01 [medline]
PHST- 2001/12/12 10:00 [entrez]
AID - S1525-0016(01)90492-7 [pii]
AID - 10.1006/mthe.2001.0492 [doi]
PST - ppublish
SO  - Mol Ther. 2001 Dec;4(6):543-50. doi: 10.1006/mthe.2001.0492.