γ/δ Receptor-expressing T-cell clones from a cutaneous T-cell lymphoma suppress hematopoiesis

Summary

Recently we described a cutaneous T-cell lymphoma expressing the γ/δ T-cell receptor [5]. The patient suffering from this lymphoma showed low numbers of myeloid and T cells in peripheral blood, while B and NK cells were relatively increased. In vitro culture of the patient's bone marrow (BM) cells revealed a significant suppression of myeloid/monocyte colony formation (GM-CFU) compared with normal controls. This was not due to infiltration of the BM with lymphoma cells. We speculated that a soluble factor either secreted or induced by the lymphoma cells might be responsible for the marked suppression of hematopoiesis in this patient. From a skin biopsy with infiltrating γ/δ T-lymphoma cells we established T-cell clones bearing the γ/δ T-cell receptor and resembling the phenotype of the lymphoma cells. The supernatant (SN) of these γ/δ T-cell clones reduced the number of colonies in a CFU-GM assay (using normal control BM) in comparison to SN of α/β T-cell clones established from the same biopsy. This suppression was seen mainly on day 7 of culture and was not neutralized by the addition of placenta-CM. The main mediator of this suppression seems to be IFN-γ,since it was detectable in high amounts in the SN of these γ/δ T-cell tumor clones as well as in the serum of the patient. In addition, anti-IFN-γ antibodies can reverse the T-cell SN-mediated suppression of CFU-GM. We conclude that high serum levels of interferon-γ, which is secreted in high amounts from γ/δ T-cells grown from a biopsy of a cutaneous lymphoma, can suppress hematopoiesis.