PMID- 10845917
OWN - NLM
STAT- MEDLINE
DCOM- 20000810
LR  - 20210216
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 95
IP  - 12
DP  - 2000 Jun 15
TI  - Increased apoptosis of peripheral blood T cells following allogeneic 
      hematopoietic cell transplantation.
PG  - 3832-9
AB  - Lymphopenia and immune deficiency are significant problems following allogeneic 
      hematopoietic cell transplantation (HCT). It is largely assumed that delayed 
      immune reconstruction is due to a profound decrease in thymus-dependent 
      lymphopoiesis, especially in older patients, but apoptosis is also known to play 
      a significant role in lymphocyte homeostasis. Peripheral T cells from patients 
      who received HCT were studied for evidence of increased cell death. Spontaneous 
      apoptosis was measured in CD3(+) T cells following a 24-hour incubation using 
      7-amino-actinomycin D in conjunction with the dual staining of cell surface 
      antigens. Apoptosis was significantly greater among CD3(+) T cells taken from 
      patients 19-23 days after transplantation (30.4% +/- 12.5%, P <.05), and 1 year 
      after transplantation (9.7% +/- 2.8%, P <.05) compared with healthy controls 
      (4.0% +/- 1.5%). Increased apoptosis occurred preferentially in HLA (human 
      leukocyte antigen)-DR positive cells and in both CD3(+)/CD4(+) and CD3(+)/CD8(+) 
      T-cell subsets, while CD56(+)/CD3(-) natural killer cells were relatively 
      resistant to apoptosis. The extent of CD4(+) T-cell apoptosis was greater in 
      patients with grade II-IV acute graft-versus-host disease (GVHD) (33. 9% +/- 
      11.3%) compared with grade 0-I GVHD (14.6 +/- 6.5%, P <.05). T-cell apoptosis was 
      also greater in patients who received transplantations from HLA-mismatched donors 
      (39.5% +/- 10.4%, P <. 05) or HLA-matched unrelated donors (32.1% +/- 11.4%, P 
      <.05) compared with patients who received transplantations from HLA-identical 
      siblings (19.6% +/- 6.7%). The intensity of apoptosis among CD4(+) T cells was 
      significantly correlated with a lower CD4(+) T-cell count. Together, these 
      observations suggest that activation of T cells in vivo, presumably by 
      alloantigens, predisposes the cells to spontaneous apoptosis, and this phenomenon 
      is associated with lymphopenia. Activation-induced T-cell apoptosis may 
      contribute to delayed immune reconstitution following HCT. (Blood. 
      2000;95:3832-3839)
FAU - Lin, M T
AU  - Lin MT
AD  - Fred Hutchinson Cancer Research Center, Division of Clinical Research, and the 
      University of Washington School of Medicine, Seattle, WA 98109-1024, USA.
FAU - Tseng, L H
AU  - Tseng LH
FAU - Frangoul, H
AU  - Frangoul H
FAU - Gooley, T
AU  - Gooley T
FAU - Pei, J
AU  - Pei J
FAU - Barsoukov, A
AU  - Barsoukov A
FAU - Akatsuka, Y
AU  - Akatsuka Y
FAU - Hansen, J A
AU  - Hansen JA
LA  - eng
GR  - AI33484/AI/NIAID NIH HHS/United States
GR  - CA15704/CA/NCI NIH HHS/United States
GR  - CA18029/CA/NCI NIH HHS/United States
GR  - etc.
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Antigens, CD)
RN  - 0 (CD3 Complex)
RN  - 0 (Fluorescent Dyes)
RN  - 0 (HLA-DR Antigens)
RN  - 1CC1JFE158 (Dactinomycin)
RN  - 7240-37-1 (7-aminoactinomycin D)
SB  - IM
MH  - Acute Disease
MH  - Adult
MH  - Antigens, CD/blood
MH  - Apoptosis/*immunology
MH  - CD3 Complex/blood
MH  - Cells, Cultured
MH  - Dactinomycin/analogs & derivatives/pharmacology
MH  - Fluorescent Dyes
MH  - Graft vs Host Disease/blood/*immunology
MH  - HLA-DR Antigens/blood
MH  - *Hematopoietic Stem Cell Transplantation
MH  - Histocompatibility Testing
MH  - Humans
MH  - In Situ Nick-End Labeling
MH  - Middle Aged
MH  - T-Lymphocytes/drug effects/*immunology/pathology
MH  - Transplantation, Homologous/*immunology
EDAT- 2000/06/14 09:00
MHDA- 2000/08/12 11:00
CRDT- 2000/06/14 09:00
PHST- 2000/06/14 09:00 [pubmed]
PHST- 2000/08/12 11:00 [medline]
PHST- 2000/06/14 09:00 [entrez]
AID - S0006-4971(20)63954-4 [pii]
PST - ppublish
SO  - Blood. 2000 Jun 15;95(12):3832-9.