Activation and expansion of CD8(+) T effector cells in patients with chronic graft-versus-host disease.

We tested the hypothesis that changes in the phenotype of CD8(+) T cells from patients with chronic graft-versus-host disease (cGVHD) correlate with disease activity, and resolve or normalize in clinically tolerant patients successfully withdrawn from immunosuppression therapy (IST). No significant difference was found in the absolute CD8(+) T cell counts among cGVHD patients, tolerant patients, and healthy controls. However, compared with healthy normal controls, CD8(+) T cells from cGVHD patients had decreased expression of the IL-7 receptor and an increase in effector T cells, Ki-67, and perforin expression and apoptosis, suggesting that activation, differentiation, and proliferation of host-reactive CD8(+) effector T cells is a mechanism by which cGVHD is sustained and persists. The increase in effector T cells was most prominent in older patients and patients who were cytomegalovirus seropositive before transplantation. Use of IST was associated with a decreased number of CD45RA(-) CD8(+) effector T cells, a decreased expression of Ki-67, and an increased expression of CD95 (Fas). Together, these results demonstrate that CD8(+) T cells in patients with cGVHD are characterized by an increased level of activation and proliferation, and an expansion of effector cells that appear to be selectively sensitive to IST compared with other CD8(+) T cells. In GVHD-free tolerant patients, CD8(+) T cells showed an increased expression of granzyme and HLA-DR molecules compared with CD8(+) T cells from healthy controls, indicating that clinical tolerance in these patients can occur without full normalization of the CD8(+) T cell phenotype.