Increased cytotoxic T cells with effector phenotype in aplastic anemia and myelodysplasia.

OBJECTIVE: We hypothesized that an active autoimmune process in aplastic anemia (AA) corresponds to the expansion of cytotoxic lymphocytes (CTLs) displaying mature effector phenotype. We determined whether the numbers of effector CTLs in blood of patients with bone marrow failure syndromes are elevated and correlate with the disease activity and responsiveness to immunosuppression. PATIENTS AND METHODS: We analyzed samples from patients with AA, myelodysplastic syndrome (MDS), polytransfused patients with nonimmune-mediated hematologic disease, and normal controls for the presence of effector T lymphocytes using four-color flow cytometry. Expression of CD57 and loss of CD28 on CD8+CD3+ CTL were used as markers for the terminal effector phenotype. In addition, intracellular staining for perforin and granzyme B was preformed. The numbers of effector CTL did not differ between healthy individuals and hematologic controls and the two groups were pooled. RESULTS: The percentages of CD8+CD28- and CD8+CD28-CD57+ cells were significantly higher in AA and MDS patients than in controls. There was a trend toward a gradual decrease in the effector CTLs from the high values observed in untreated new patients and patients who did not respond to immunosuppression, intermediate levels for partial responders and complete responders, to the lowest levels seen in controls. However, severity of pancytopenia did not correlate with the size of the effector cell population. In contrast to CD57+ CTLs, expression of perforin or granzyme B in the cytotoxic effector cells did not differ in AA patients from those of controls. CONCLUSIONS: Our results indicate that phenotypically defined effector CTLs are increased in AA and MDS and the effector phenotype may be useful to isolate and characterize antigen-specific T cells in AA in order to delineate the possible inciting or driving agents in AA.