Treatment of pure red cell aplasia with ciclosporin: suppression of activated T suppressor/cytotoxic and NK-like cells in marrow and blood correlates with haematological response.

In pure red cell aplasia (PRCA), suppression of erythropoiesis is most probably effected by cellular and/or antibody-mediated immune mechanisms. We have prospectively investigated the patterns of activated T-lymphocyte subsets and natural killer (NK)-like cells in the bone marrow (BM) and peripheral blood (PB) of 6 PRCA patients prior to and during treatment with the T-cell selective immunosuppressive drug Ciclosporin (CS; Cyclosporin-A). Before CS therapy, large proportions of circulating activated HLA-DR+ T-suppressor/cytotoxic cells (28%, 11-41; median and range), DR+ T-helper cells (7%, 4-13) and cytoplasmic interferon-gamma+ (IFN-gamma) lymphocytes (20%, 9-33) were found in PRCA, but were barely detectable in healthy controls. Similarly, high levels of activated T cells were present in patient marrows. Initiation of CS therapy resulted in rapidly decreasing levels of activated T cells and NK cells both in PB and in BM. During follow-up of individual patients, an inverse relationship was observed between the haematological response to CS and the levels of activated T-suppressor/cytotoxic cells, IFN-gamma+ lymphocytes (in PB and BM) and NK-like cells (in BM). The present correlations indicate a pathogenetic role of phenotypically activated T-suppressor/cytotoxic cells and possibly NK-like cells in PRCA. During successful treatment with CS, these cell types are reduced in numbers but reappear in relapse. Our results also pinpoint the clinical value of monitoring activated T-cell subsets for the prediction of immunological remission in PRCA and related disorders.