Increased cytotoxic T cells with effector phenotype in aplastic anemia andmyelodysplasia

Objective. We hypothesized that an active autoimmune process in aplastic an emia (AA) corresponds to the expansion of cytotoxic lymphocytes (CTLs) disp laying mature effector phenotype. We determined whether the numbers of effe ctor CTLs in blood of patients with bone marrow failure syndromes are eleva ted and correlate with the disease activity and responsiveness to immunosup pression. Patients and Methods. We analyzed samples from patients with AA, myelodyspl astic syndrome (MDS), polytransfused patients with nonimmune-mediated hemat ologic disease, and normal controls for the presence of effector T lymphocy tes using four-color How 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 preform ed. 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 we re 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 imm unosuppression, intermediate levels for partial responders and complete res ponders, to the lowest levels seen in controls. However, severity of pancyt openia did not correlate with the size of the effector cell population. In contrast to CD57(+) CTLs, expression of perforin or granzyme B in the cytot oxic 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 is olate and characterize antigen-specific T cells in AA in order to delineate the possible inciting or driving agents in AA. (C) 2001 International Soci ety for Experimental Hematology. Published by Elsevier Science Inc.