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Blood, Vol. 95 No. 12 (June 15), 2000:
pp. 3832-3839
Increased apoptosis of peripheral blood T cells following
allogeneic hematopoietic cell transplantation
Ming-Tseh Lin,
Li-Hui Tseng,
Haydar Frangoul,
Ted Gooley,
Ji Pei,
Alexandre Barsoukov,
Yoshiki Akatsuka, and
John A. Hansen
From the Fred Hutchinson Cancer Research Center, Division of
Clinical Research, and the University of Washington School of Medicine,
Seattle, WA; and the National Taiwan University Hospital, Department of
Oncology and Medical Genetics, Taipei, Taiwan.
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.
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