PMID- 18981100
OWN - NLM
STAT- MEDLINE
DCOM- 20081212
LR  - 20190516
IS  - 1550-6606 (Electronic)
IS  - 0022-1767 (Linking)
VI  - 181
IP  - 10
DP  - 2008 Nov 15
TI  - The host environment regulates the function of CD8+ graft-versus-host-reactive 
      effector cells.
PG  - 6820-8
AB  - We have examined how the host environment influences the graft-vs-leukemia (GVL) 
      response following transfer of donor T cells to allogeneic chimeras. Donor T 
      cells induce significant GVL when administered in large numbers to established 
      mixed chimeras (MC). However, when using limiting numbers of T cells, we found 
      that late transfer to MC induced less GVL than did early transfer to freshly 
      irradiated allogeneic recipients. Late donor T cell transfer to MC was associated 
      with marked accumulation of anti-host CD8 cells within the spleen, but delayed 
      kinetics of differentiation, reduced expression of effector molecules including 
      IFN-gamma, impaired cytotoxicity, and higher rates of sustained apoptosis. 
      Furthermore, in contrast to the spleen, we observed a significant delay in donor 
      CD8 cell recruitment to the bone marrow, a key location for hematopoietic tumors. 
      Increasing the numbers of T cells transferred to MC led to the enhancement of CTL 
      activity and detectable increases in absolute numbers of IFN-gamma(+) cells 
      without inducing graft-vs-host disease (GVHD). TLR-induced systemic inflammation 
      accelerated differentiation of functional CTL in MC but was associated with 
      severe GVHD. In the absence of inflammation, both recipient T and non-T cell 
      populations impeded the full development of GVHD-inducing effector function. We 
      conclude that per-cell deficits in the function of donor CD8 cells activated in 
      MC may be overcome by transferring larger numbers of T cells without inducing 
      GVHD.
FAU - Chakraverty, Ronjon
AU  - Chakraverty R
AD  - Transplantation Immunology Group, Department of Hematology, University College 
      London, London, UK.
FAU - Flutter, Barry
AU  - Flutter B
FAU - Fallah-Arani, Farnaz
AU  - Fallah-Arani F
FAU - Eom, Hyeon-Seok
AU  - Eom HS
FAU - Means, Terry
AU  - Means T
FAU - Andreola, Giovanna
AU  - Andreola G
FAU - Schwarte, Sebastian
AU  - Schwarte S
FAU - Buchli, Jennifer
AU  - Buchli J
FAU - Cotter, Pete
AU  - Cotter P
FAU - Zhao, Guiling
AU  - Zhao G
FAU - Sykes, Megan
AU  - Sykes M
LA  - eng
GR  - P01 CA111519/CA/NCI NIH HHS/United States
GR  - R01 CA79989/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
SB  - IM
MH  - Animals
MH  - Bone Marrow Transplantation/*methods
MH  - CD8-Positive T-Lymphocytes/*immunology
MH  - Flow Cytometry
MH  - Graft vs Host Disease/*immunology
MH  - Graft vs Leukemia Effect/*immunology
MH  - Lymphocyte Activation/immunology
MH  - Mice
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - T-Lymphocytes/transplantation
MH  - Transplantation Chimera/immunology
EDAT- 2008/11/05 09:00
MHDA- 2008/12/17 09:00
CRDT- 2008/11/05 09:00
PHST- 2008/11/05 09:00 [pubmed]
PHST- 2008/12/17 09:00 [medline]
PHST- 2008/11/05 09:00 [entrez]
AID - 181/10/6820 [pii]
AID - 10.4049/jimmunol.181.10.6820 [doi]
PST - ppublish
SO  - J Immunol. 2008 Nov 15;181(10):6820-8. doi: 10.4049/jimmunol.181.10.6820.