Malignant chronic lymphocytic leukemia B cells elaborate soluble factors that down‐regulate T cell and NK function

To determine if the frequently observed T celt and natural kitler dysfunction in B‐chronic lymphocytic leukemia might be related to the presence of large numbers of malignant B cells, we studied the effects of secretory or shed products of CLL B cells on normal (control) T cell and NK function. The cell‐free supernatants from CLL B cells cultured from 24 to 48 hr inhibited a variety of T cell functions including: PHA‐induced proliferation, PHA‐stimulated entry of T cells into the cell cycle, and PHA‐induced production of interleukin‐2. In addition, B‐CLL supernatants diminished control NK activity. Purified control B cells and other malignant cell lines produced little or no inhibitory activity toward these T cell or NK functions. The sera from these same B‐CLL patients diminished PHA‐induced interleukin‐2 production by control T cells. Initial molecular characterization of the inhibitory factor(s) revealed it to be of low molecular weight (< 5000 daltons) with loss of functional activity after treatment with neuraminidase. This suggested that this substance might be either a ganglioside or glycoprotein whose inhibitory activity depends on the presence of a sialic acid moiety. If CLL B celts are capable of secreting or shedding immunosuppressive factors), then alteration of this property may result in a more normal immune system for these patients.