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

To determine if the frequently observed T cell and natural killer 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 (less than 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 cells are capable of secreting or shedding immunosuppressive factor(s), then alteration of this property may result in a more normal immune system for these patients.