CD8+/DR+/CD25--T-lymphocytes associated with marrow graft failure

Phenotypic and functional characteristics of peripheral blood mononuclear cells (PBMC) were studied in eight patients with poor graft function following HLA-identical T cell-depleted marrow transplantation. Similar patients with good graft function and normal individuals were used as controls. Freshly isolated PBMC from patients with failing grafts contained more CD3+ and CD8+ cells than PBMC from well engrafted patients. The CD8+ cells appeared activated insofar as they expressed DR antigens, but they did not express the low affinity IL-2 receptor recognized by Tac antibody (CD25) and they did not have increased cytolytic activities. After culture with phytohemagglutinin (PHA) and IL-2, PBMC from patients with poor graft function contained fewer CD2+ and CD4+ cells than cultured PBMC from patients with good graft function. Cultured cells from patients with poor graft function acquired lymphokine activated killer (LAK) activity against NK-sensitive and NK-insensitive targets, but still did not express CD25. Host-mediated anti-donor cytotoxic activity could be demonstrated in one patient only after presensitization with donor cells and culture with IL-2 and PHA. The abnormalities in T cell activation observed in patients with poor graft function did not correlate with the donor or host origin of lymphoid cells. These data indicate that some cases of graft failure may be associated with defective T cell maturation. These abnormalities may simply represent a consequence of marrow failure or they may actually contribute to failure by not providing critical hematopoietic accessory functions.