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, John A. Hansen

Research output: Contribution to journalArticle

60 Citations (Scopus)

Abstract

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 0-1 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 lymphopenla. Activation-induced T-cell apoptosis may contribute to delayed immune reconstitution following HCT. (C) 2000 by The American Society of Hematology.

Original languageEnglish
Pages (from-to)3832-3839
Number of pages8
JournalBlood
Volume95
Issue number12
Publication statusPublished - 15-06-2000

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T-cells
Cell Transplantation
Blood Cells
Blood
Apoptosis
T-Lymphocytes
HLA Antigens
Transplantation
Graft vs Host Disease
Grafts
Chemical activation
Lymphopoiesis
Thymus
Unrelated Donors
Lymphopenia
Isoantigens
Lymphocytes
T-Lymphocyte Subsets
Cell death
Surface Antigens

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Lin, M. T., Tseng, L. H., Frangoul, H., Gooley, T., Pei, J., Barsoukov, A., ... Hansen, J. A. (2000). Increased apoptosis of peripheral blood T cells following allogeneic hematopoietic cell transplantation. Blood, 95(12), 3832-3839.
Lin, Ming Tseh ; Tseng, Li Hui ; Frangoul, Haydar ; Gooley, Ted ; Pei, Ji ; Barsoukov, Alexandre ; Akatsuka, Yoshiki ; Hansen, John A. / Increased apoptosis of peripheral blood T cells following allogeneic hematopoietic cell transplantation. In: Blood. 2000 ; Vol. 95, No. 12. pp. 3832-3839.
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abstract = "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 0-1 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 lymphopenla. Activation-induced T-cell apoptosis may contribute to delayed immune reconstitution following HCT. (C) 2000 by The American Society of Hematology.",
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Lin, MT, Tseng, LH, Frangoul, H, Gooley, T, Pei, J, Barsoukov, A, Akatsuka, Y & Hansen, JA 2000, 'Increased apoptosis of peripheral blood T cells following allogeneic hematopoietic cell transplantation', Blood, vol. 95, no. 12, pp. 3832-3839.

Increased apoptosis of peripheral blood T cells following allogeneic hematopoietic cell transplantation. / Lin, Ming Tseh; Tseng, Li Hui; Frangoul, Haydar; Gooley, Ted; Pei, Ji; Barsoukov, Alexandre; Akatsuka, Yoshiki; Hansen, John A.

In: Blood, Vol. 95, No. 12, 15.06.2000, p. 3832-3839.

Research output: Contribution to journalArticle

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T1 - Increased apoptosis of peripheral blood T cells following allogeneic hematopoietic cell transplantation

AU - Lin, Ming Tseh

AU - Tseng, Li Hui

AU - Frangoul, Haydar

AU - Gooley, Ted

AU - Pei, Ji

AU - Barsoukov, Alexandre

AU - Akatsuka, Yoshiki

AU - Hansen, John A.

PY - 2000/6/15

Y1 - 2000/6/15

N2 - 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 0-1 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 lymphopenla. Activation-induced T-cell apoptosis may contribute to delayed immune reconstitution following HCT. (C) 2000 by The American Society of Hematology.

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 0-1 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 lymphopenla. Activation-induced T-cell apoptosis may contribute to delayed immune reconstitution following HCT. (C) 2000 by The American Society of Hematology.

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Lin MT, Tseng LH, Frangoul H, Gooley T, Pei J, Barsoukov A et al. Increased apoptosis of peripheral blood T cells following allogeneic hematopoietic cell transplantation. Blood. 2000 Jun 15;95(12):3832-3839.