TRANSFORMING GROWTH-FACTOR-BETA-1 (TGF-BETA-1) RELEASED BY AN EPSTEIN-BARR-VIRUS (EBV) POSITIVE SPONTANEOUS LYMPHOBLASTOID CELL-LINE FROM APATIENT WITH KOSTMANN CONGENITAL NEUTROPENIA INHIBITS THE GROWTH OF NORMAL COMMITTED HEMATOPOIETIC PROGENITORS IN-VITRO

This study reports the characterization of a spontaneous lymphoblastoi d cell line (LCL) raised from the peripheral blood of a patient with K ostmann's congenital neutropenia. The LCL was composed of EBV-infected polyclonal B cells and displayed surface markers and pattern of growt h in vitro typical of normal LCLs. The supernatant of the LCL containe d a colony inhibiting activity (CIA) that decreased the cloning effici ency of normal committed haemopoietic progenitors and was identified a s immunoreactive transforming growth factor beta1 (TGF-beta1) by neutr alization experiments with a specific antiserum. Control studies with a panel of LCLs spontaneously derived from the peripheral blood of pat ients seropositive for Epstein-Barr virus (EBV) infections showed that 5/ 30 LCLs produced a CIA. This CIA was not identifiable as TGF-beta1 but rather was due to the combined effects of tumour necrosis factor alpha (TNFalpha), tumour necrosis factor beta (TNFbeta) and interferon alpha (IFNalpha), that were present in the LCL supernatants. The hypo thesis that the B cells latently infected by EBV in vivo and possibly expanded as a consequence of the infection may have contributed to the inhibition of the patient granulopoiesis by releasing TGF-beta1 will be discussed.