Inhibition of CFU-GM by prostaglandins in a case of chronic T-cell lymphocytosis and neutropenia.
A 45-year-old Caucasian female with seropositive rheumatoid arthritis was found coincidentally to have a circulating lymphocytosis (6.4 x 10(9)/l) and neutropenia (0.1 x 10(9)/l). Initial presentation was with mouth ulceration and recurrent infections. A spleen scan showed no evidence of splenomegaly and serum titres against EBV, CMV and toxoplasmosis were negative. No anti-neutrophil antibodies were found. Marrow aspiration demonstrated a lymphocytosis of 60% with reduced numbers of granular precursors. Lymphocytes in both blood and bone marrow were CD3, CD8, CD16 and HLA-DR positive. Lymphocyte conditioned medium (LCM) generated from the patient's blood lymphocytes (without phytohaemagglutinin) was found to inhibit allogeneic colony-forming unit, granulocyte-macrophage (CFU-GM) stem cells in semi-solid culture compared with control LCM. This inhibitory activity was abrogated by the cytolytic removal of CD8 cells prior to LCM production and was significantly reduced by co-culture with indomethacin. Culture of the patient's marrow at autostimulatory light density marrow cell concentrations showed poor spontaneous CFU-GM colony formation until marrow CD8 lymphocytes were removed cytolytically. Prednisolone was used therapeutically (40 mg/d) and resulted in the patient's neutrophil count rising from 0.06 x 10(9)/l to 1.1 x 10(9)/l and a fall in the total lymphocyte count to 1.9 x 10(9)/l. Reevaluation of the patient's LCM post steroid therapy showed loss of the previous inhibitory effect. The patient's neutrophil count is maintained on oral azathioprine and indomethacin.
Smith
J G
JG
Department of Haematology, Royal United Hospital, Bath.
Smith
M A
MA
James
I
I
Blundell
E
E
Maddison
P J
PJ
D000380:Agranulocytosis / Q000473:pathology*; D002478:Cells, Cultured; D002908:Chronic Disease; D005260:Female; D006098:Granulocytes / Q000473:pathology*; D006412:Hematopoietic Stem Cells / Q000473:pathology*; D006801:Humans; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008218:Lymphocytosis / Q000378:metabolism / Q000473:pathology*; D008264:Macrophages / Q000473:pathology*; D008875:Middle Aged; D009503:Neutropenia / Q000378:metabolism / Q000473:pathology*; D011453:Prostaglandins / Q000502:physiology*; D013601:T-Lymphocytes / Q000473:pathology
D011453:Prostaglandins; D007213:Indomethacin