Spontaneous responsiveness to cytokines by human T-cell leukemias

The molecular basis for autonomous growth of malignant forms of human T lymphocytes is not known. It can be investigated by functional responses of malignant cells in comparison with untransformed counterparts. At least two pathways (the CD2 and CD3 pathways) of human T-cell activation have been recently defined on the basis of monoclonal antibody activities in vitro, an experimental model exists which can be used to investigate which pathway of T-cell triggering might be involved in malignant growth. In untransformed T lymphocytes, responses to addition of cytokines are strictly controlled by signals which are mediated through triggering molecules including CD2 and CD3 and we therefore investigated 20 freshly recovered human T leukemias with regard to spontaneous growth in response to interleukins. The majority of cases (16 out of 20) investigated displayed spontaneous responsiveness to cytokines (interleukins 1, 4, and 6), which might be related to activation signals mediated through the CD2 pathway. The functional repertoire of T leukemias did not correlate with expression of differentiation antigens conventionally employed for leukemia typing.