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

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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.

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

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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., Akatsuka, Y., & Hansen, J. A. (2000). Increased apoptosis of peripheral blood T cells following allogeneic hematopoietic cell transplantation. Blood, 95(12), 3832-3839.