Increased apoptosis of peripheral blood T cells following allogeneic hematopoietic cell transplantation.
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)
Lin
M T
MT
Fred Hutchinson Cancer Research Center, Division of Clinical Research, and the University of Washington School of Medicine, Seattle, WA 98109-1024, USA.
Tseng
L H
LH
Frangoul
H
H
Gooley
T
T
Pei
J
J
Barsoukov
A
A
Akatsuka
Y
Y
Hansen
J A
JA
D000208:Acute Disease; D000328:Adult; D015703:Antigens, CD / Q000097:blood; D017209:Apoptosis / Q000276:immunology*; D017252:CD3 Complex / Q000097:blood; D002478:Cells, Cultured; D003609:Dactinomycin / Q000031:analogs & derivatives / Q000494:pharmacology; D005456:Fluorescent Dyes; D006086:Graft vs Host Disease / Q000097:blood / Q000276:immunology*; D006684:HLA-DR Antigens / Q000097:blood; D018380:Hematopoietic Stem Cell Transplantation; D006650:Histocompatibility Testing; D006801:Humans; D020287:In Situ Nick-End Labeling; D008875:Middle Aged; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D014184:Transplantation, Homologous / Q000276:immunology*
D015703:Antigens, CD; D017252:CD3 Complex; D005456:Fluorescent Dyes; D006684:HLA-DR Antigens; D003609:Dactinomycin; C025942:7-aminoactinomycin D