PMID- 14633734
OWN - NLM
STAT- MEDLINE
DCOM- 20040209
LR  - 20171116
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 63
IP  - 22
DP  - 2003 Nov 15
TI  - Antitumor activity mediated by double-negative T cells.
PG  - 8014-21
AB  - Allogeneic lymphocytes are potent mediators of leukemia and lymphoma remission. 
      The goal of this study was to determine whether single MHC class I 
      locus-mismatched lymphocytes could generate an antilymphoma activity in the 
      absence of graft-versus-host-disease (GVHD) and to understand the underlying 
      mechanisms. Immunoincompetent Scid or lethally irradiated mice were challenged 
      i.v. with a lethal dose of A20 lymphoma cells together with an infusion of single 
      MHC class I locus mismatched splenocytes. Mice that were challenged with A20 
      cells alone succumbed to lymphoma between 34 and 50 days after infusion. In 
      contrast, >75% of mice that were coinfused with single class I MHC locus 
      mismatched splenocytes survived indefinitely (n = 20) in the absence of GVHD. 
      Interestingly, the number of CD3(+)CD4(-)CD8(-) double-negative (DN) T cells 
      increased 15-fold in mice that did not develop lymphoma. Both DN T cells isolated 
      from the spleens of lymphoma-free mice and DN T cells cloned from naive mice were 
      cytotoxic to A20 lymphoma cells in vitro. When DN T cell clones were infused into 
      naive mice i.v. together with A20 lymphoma cells, 86% of recipient mice were 
      protected from lymphoma onset and did not develop GVHD (n = 22). To assess 
      whether the systemic injection of DN T cells can also suppress local tumor 
      development, A20 cells were infused i.m., and at the same time DN T cell clones 
      were infused either i.v. or i.m. Results indicated that DN T cells infused 
      systemically (i.v.) could not prevent local tumor outgrowth, but DN T cells 
      coinfused locally (i.m.) prevented local tumor development in 91% of animals (n = 
      11). Furthermore, we demonstrate that primary DN T cells were also able to 
      prevent tumor growth in 75% of mice when infused together with A20 cells i.m. (n 
      = 12). Together, these results demonstrate that an antilymphoma activity can be 
      generated in mice without causing GVHD. Furthermore, DN T cells can suppress 
      lymphoma cells in vivo and in vitro, suggesting that DN T cells could be used as 
      a novel strategy for the treatment of lymphoma.
FAU - Young, Kevin J
AU  - Young KJ
AD  - Department of Laboratory Medicine and Pathobiology, Multi Organ Transplantation 
      Program, Toronto General Research Institute, University Health Network, 621 
      University Avenue, Toronto, Ontario M5G 2C4, Canada.
FAU - Kay, Lyndsey S
AU  - Kay LS
FAU - Phillips, M James
AU  - Phillips MJ
FAU - Zhang, Li
AU  - Zhang L
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (Fas Ligand Protein)
RN  - 0 (Fasl protein, mouse)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (fas Receptor)
SB  - IM
MH  - Animals
MH  - Fas Ligand Protein
MH  - Graft vs Host Disease/immunology
MH  - Histocompatibility Antigens Class I/immunology
MH  - Immunocompromised Host/immunology
MH  - Immunotherapy, Adoptive/*methods
MH  - Lymphoma/*immunology/prevention & control/therapy
MH  - Membrane Glycoproteins/immunology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - Mice, SCID
MH  - Mice, Transgenic
MH  - T-Lymphocytes/*immunology
MH  - fas Receptor/immunology
EDAT- 2003/11/25 05:00
MHDA- 2004/02/11 05:00
CRDT- 2003/11/25 05:00
PHST- 2003/11/25 05:00 [pubmed]
PHST- 2004/02/11 05:00 [medline]
PHST- 2003/11/25 05:00 [entrez]
PST - ppublish
SO  - Cancer Res. 2003 Nov 15;63(22):8014-21.