PMID- 8930658
OWN - NLM
STAT- MEDLINE
DCOM- 19970221
LR  - 20211203
IS  - 1043-0342 (Print)
IS  - 1043-0342 (Linking)
VI  - 7
IP  - 16
DP  - 1996 Oct 20
TI  - Gene transfer of transforming growth factor-beta 1 prolongs murine cardiac 
      allograft survival by inhibiting cell-mediated immunity.
PG  - 1981-8
AB  - Delivery of immunosuppressants directly to allografts using gene transfer and 
      gene therapy approaches may inhibit immune activation while avoiding the systemic 
      toxicity of conventional immunosuppression. Cardiac grafts from allogeneic 
      (C57BL/6, H-2b) donors were transplanted into CBA/J (H-2k) recipients in a 
      heterotopic, non-vascularized model pSVTGF-beta 1, a plasmid encoding murine 
      transforming growth factor-beta 1 (TGF-beta 1) under the control of an SV40 
      promoter, was directly injected into grafts at surgery and prolonged survival 
      from 12.0 +/- 0.7 to 25.1 +/- 2.1 days (p < 0.001) in a dose-dependent manner. 
      Plasmid gene transfer-induced immunosuppression was localized to the area of the 
      graft because plasmid injected remote from the graft did not prolong allograft 
      survival and systemic immunity was not influenced by local gene transfer. 
      Limiting dilution analysis of graft-infiltrating cells demonstrated that gene 
      transfer reduced the precursor frequency of donor-specific cytotoxic T 
      lymphocytes (CTL) and activated and total interleukin-2 (IL-2) producing helper T 
      lymphocytes (HTL) in graft-infiltrating cells, whereas CTL generation and HTL 
      precursor frequency in splenic lymphocytes were not altered. Additional data 
      revealed that gene transfer inhibited the priming of TH0 cells and the conversion 
      of primed TH1 cells to activated cells without the participation of TH2 
      suppressors. These data demonstrate that gene transfer of plasmid DNA encoding 
      TGF-beta 1 in vivo suppresses local T cell immunity, which prolongs allograft 
      survival.
FAU - Qin, L
AU  - Qin L
AD  - Department of Surgery, University of Michigan, Ann Arbor 48109, USA.
FAU - Ding, Y
AU  - Ding Y
FAU - Bromberg, J S
AU  - Bromberg JS
LA  - eng
GR  - P60-AR20557/AR/NIAMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Hum Gene Ther
JT  - Human gene therapy
JID - 9008950
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Interleukin-2)
RN  - 0 (Transforming Growth Factor beta)
SB  - IM
MH  - Animals
MH  - Female
MH  - *Gene Transfer Techniques
MH  - Heart Transplantation/*immunology
MH  - Immunity, Cellular/immunology
MH  - Immunosuppression Therapy
MH  - Immunosuppressive Agents/*immunology
MH  - Interleukin-2/biosynthesis
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - Mice, Inbred CBA
MH  - T-Lymphocytes, Cytotoxic/*immunology
MH  - T-Lymphocytes, Helper-Inducer/*immunology
MH  - Transforming Growth Factor beta/genetics/*immunology
MH  - Transplantation, Homologous
EDAT- 1996/10/20 00:00
MHDA- 1996/10/20 00:01
CRDT- 1996/10/20 00:00
PHST- 1996/10/20 00:00 [pubmed]
PHST- 1996/10/20 00:01 [medline]
PHST- 1996/10/20 00:00 [entrez]
AID - 10.1089/hum.1996.7.16-1981 [doi]
PST - ppublish
SO  - Hum Gene Ther. 1996 Oct 20;7(16):1981-8. doi: 10.1089/hum.1996.7.16-1981.