COSTIMULATION OF CUTANEOUS T-CELL LYMPHOMA-CELLS BY INTERLEUKIN-7 AND INTERLEUKIN-2 - POTENTIAL AUTOCRINE OR PARACRINE EFFECTORS IN THE SEZARY-SYNDROME

Purpose: To examine interleukin-7 (IL7)- and interleukin-2 (IL2)-induced proliferation of Sezary lymphoma cells and to consider if an autocrine or paracrine growth-stimulatory circuit involving IL7 exists in the Sezary syndrome (SS). Materials and methods: Fresh Sezary lymphoma cells were maintained in short-term culture in the presence of cytokines, and growth was measured by incorporation of (3H)-thymidine (TdR). Expression of IL7 and IL7 and IL2 receptors (IL7-R and IL2-R, respectively) was assessed by polymerase chain amplification of first-strand complementary DNA (RT-PCR), by affinity cross-linking of radioactive iodine-T25-IL7, and by dual-color fluorescence- activated cell analysis. IL-7 production was measured by immunoassay. Results: Sezary lymphoma cells from seven patients showed synergistic (five of seven) or additive (two of seven) proliferation when cultured in the presence of IL2 and IL7, as compared with culture with either cytokine alone. Two patients with evidence of synergistic stimulation of [3H]-TdR incorporation showed IL7-R gene expression by RT-PCR and IL7 affinity cross- linking. Incubation of all seven patients' cells with IL7 induced coexpression to varying degrees of IL7-R and IL2-R. Sezary lymphoma cells from at least three of five patients studied expressed IL7 mRNA, and skin from three of five patients studied, as well as normal skin, expressed IL7 mRNA by RT-PCR. Conclusion: Sezary lymphoma cells respond by proliferation to IL7 plus IL2, and in some instances produce IL7. Therapeutic maneuvers should be pursued to take advantage of this potential autocrine or paracrine growth- stimulatory mechanism.