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

Lymphopenia and immune deficiency are significant problems following alloge neic hematopoietic cell transplantation (HCT), It is largely assumed that d elayed immune reconstruction is due to a profound decrease in thymus-depend ent lymphopoiesis, especially in older patients, but apoptosis is also know n 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 st aining 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 < .0 5) compared with healthy controls (4.0% +/- 1.5%), Increased apoptosis occu rred 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 o f CD4(+) T-cell apoptosis was greater in patients with grade II-IV acute gr aft-versus-host disease (GVHD)(33.9% +/- 11.3%) compared with grade 0-1 GVH D (14.6 +/- 6.5%, P < .05), T-cell apoptosis was also greater in patients w ho 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 (1 9.6% +/- 6.7%), The intensity of apoptosis among CD4(+) T cells was signifi cantly correlated with a lower CD4(+) T-cell count. Together, these observa tions suggest that activation of T cells in vivo, presumably by alloantigen s, predisposes the cells to spontaneous apoptosis, and this phenomenon is a ssociated with lymphopenia, Activation-induced T-cell apoptosis may contrib ute to delayed immune reconstitution following HCT. (C) 2000 by The America n Society of Hematology.