PMID- 17202345
OWN - NLM
STAT- MEDLINE
DCOM- 20070222
LR  - 20190516
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 178
IP  - 2
DP  - 2007 Jan 15
TI  - Donor CD8+ T cells mediate graft-versus-leukemia activity without clinical signs 
      of graft-versus-host disease in recipients conditioned with anti-CD3 monoclonal 
      antibody.
PG  - 838-50
AB  - Donor CD8(+) T cells play a critical role in mediating graft-vs-leukemia (GVL) 
      activity, but also induce graft-vs-host disease (GVHD) in recipients conditioned 
      with total body irradiation (TBI). In this study, we report that injections of 
      donor C57BL/6 (H-2(b)) or FVB/N (H-2(q)) CD8(+) T with bone marrow cells induced 
      chimerism and eliminated BCL1 leukemia/lymphoma cells without clinical signs of 
      GVHD in anti-CD3-conditioned BALB/c (H-2(d)) recipients, but induced lethal GVHD 
      in TBI-conditioned recipients. Using in vivo and ex vivo bioluminescent imaging, 
      we observed that donor CD8(+) T cells expanded rapidly and infiltrated GVHD 
      target tissues in TBI-conditioned recipients, but donor CD8(+) T cell expansion 
      in anti-CD3-conditioned recipients was confined to lymphohematological tissues. 
      This confinement was associated with lack of up-regulated expression of 
      alpha(4)beta(7) integrin and chemokine receptors (i.e., CXCR3) on donor CD8(+) T 
      cells. In addition, donor CD8(+) T cells in anti-CD3-conditioned recipients were 
      rendered unresponsive, anergic, Foxp3(+), or type II cytotoxic T phenotype. Those 
      donor CD8(+) T cells showed strong suppressive activity in vitro and mediated GVL 
      activity without clinical signs of GVHD in TBI-conditioned secondary recipients. 
      These results indicate that anti-CD3 conditioning separates GVL activity from 
      GVHD via confining donor CD8(+) T cell expansion to host lymphohemological 
      tissues as well as tolerizing them in the host.
FAU - Zhang, Chunyan
AU  - Zhang C
AD  - Beckman Research Institute, City of Hope National Medical Center, 1500 East 
      Duarte Road, Duarte, CA 91010, USA.
FAU - Lou, Jingwei
AU  - Lou J
FAU - Li, Nainong
AU  - Li N
FAU - Todorov, Ivan
AU  - Todorov I
FAU - Lin, Chia-Lei
AU  - Lin CL
FAU - Cao, Yu-An
AU  - Cao YA
FAU - Contag, Christopher H
AU  - Contag CH
FAU - Kandeel, Fouad
AU  - Kandeel F
FAU - Forman, Stephen
AU  - Forman S
FAU - Zeng, Defu
AU  - Zeng D
LA  - eng
GR  - K01 DK 071716/DK/NIDDK NIH HHS/United States
GR  - R21 DK 71002/DK/NIDDK NIH HHS/United States
GR  - R24 CA 92862/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (CD3 Complex)
SB  - IM
MH  - Animals
MH  - Antibodies, Monoclonal/*immunology
MH  - CD3 Complex/*immunology
MH  - CD8-Positive T-Lymphocytes/cytology/*immunology
MH  - Cell Proliferation
MH  - Graft vs Host Disease/*immunology
MH  - Leukemia/*immunology/pathology
MH  - Lymphoid Tissue/immunology/pathology
MH  - Mice
MH  - Time Factors
MH  - *Tissue Donors
MH  - Transplantation Chimera/immunology
MH  - Up-Regulation
EDAT- 2007/01/05 09:00
MHDA- 2007/02/23 09:00
CRDT- 2007/01/05 09:00
PHST- 2007/01/05 09:00 [pubmed]
PHST- 2007/02/23 09:00 [medline]
PHST- 2007/01/05 09:00 [entrez]
AID - 178/2/838 [pii]
AID - 10.4049/jimmunol.178.2.838 [doi]
PST - ppublish
SO  - J Immunol. 2007 Jan 15;178(2):838-50. doi: 10.4049/jimmunol.178.2.838.