Impairment of lymphocyte function in patients with myelodysplastic syndrome and its correction by addition of Ca2+ ionophore and phorbol myristate acetate.
T and B cell functions were evaluated in eight patients with myelodysplastic syndrome (MDS). We studied the response to stimulation with phytohemagglutinin, concanavalin A, and anti-CD3 monoclonal antibody (OKT3 mAb), and found impairment of response in T cells from MDS patients in comparison with age-matched controls. The decreased proliferative response was not restored by combining normal T cells with monocytes from MDS patients, or by using T cells from MDS patients together with normal monocytes. Furthermore, proliferative responses in the autologous and allogenic mixed lymphocyte reactions were significantly decreased in MDS patients. B cells from MDS patients incorporated significantly less tritiated thymidine than B cells from controls when stimulated with Staphylococcus aureus Cowan I (SAC), and SAC stimulation failed to cause efficient immunoglobulin production by MDS B cells. However, T cells from MDS patients reacted normally when stimulated by phorbol myristate acetate plus a Ca2+ ionophore (ionomycin). Abnormal lymphocyte function may contribute to the failure of hematopoietic regulation and may thus play an important role in the pathogenesis of MDS. The finding that the addition of specific signals allowed the stimulation pathway to function may have important therapeutic implications.
Tsuchida
T
T
Department of Internal Medicine, Shimane Medical University, Japan.
Sakane
T
T
Ishikura
H
H
Tsunematsu
T
T
D000368:Aged; D000369:Aged, 80 and over; D006801:Humans; D015759:Ionomycin / Q000494:pharmacology*; D008137:Longitudinal Studies; D008214:Lymphocytes / Q000187:drug effects*; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000097:blood*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D015759:Ionomycin; D013755:Tetradecanoylphorbol Acetate