Pure red cell aplasia associated with expansion of CD3+ CD8+ granular lymphocytes expressing cytotoxicity against HLA-E+ cells

T-cell granular lymphocyte-proliferative disorder (T-GLPD) is characterized by the proliferation of cytotoxic T lymphocytes, and is often associated with pure red cell aplasia (PRCA). The mechanism involved in the development of PRCA in T-GLPD is unknown. Peripheral blood mononuclear cells were isolated from 20 patients with T-GLPD. Ten patients had associated PRCA. Granular lymphocytes (GLs) of T-GLPD are positive for CD94, but not NKG2A. To clarify the functional role of CD94 in T-GLPD, we performed a cytotoxicity assay against the trophoblast cell line, BeWo, which is known to express human leucocyte antigen (HLA)-E, a natural ligand of CD94, and is deficient in other HLA class I and class II antigens. GLs isolated from T-GLPD with PRCA patients killed BeWo cells more significantly than GLs from T-GLPD without PRCA patients. Furthermore, GLs from T-GLPD with PRCA were significantly stimulated by a monoclonal antibody against CD94, whereas those of T-GLPD without PRCA were not. Taken together, HLA-E, a ligand of CD94, was suggested to stimulate CD94+ cells to kill HLA-E+ cells in T-GLPD with PRCA. GLs of T-GLPD with PRCA have a potential positive activity against HLA-E+ cells, whereas GLs from T-GLPD without PRCA do not. CD94 may play a key role in the pathogenesis of PRCA in T-GLPD.