CELLULAR IMMUNE-RESPONSES TO AUTOLOGOUS CHRONIC MYELOGENOUS LEUKEMIA-CELLS IN-VITRO

Using a modification of the autologous mixed lymphocyte/tumour cell cu lture (MLTC), it is demonstrated here that lymphocytes from chronic-ph ase myelogenous leukaemia (CML) patients (n = 58), but not from their HLA-identical siblings, proliferated upon coculture with autologous tu mour cells. However, in most cases, the level of proliferation measure d was low (stimulation index <3, n = 37). This was most likely related to the amount of interleukin-10 (IL-10) released into the culture med ium by the CML cells, because addition of neutralizing anti-IL-10 seru m to MLTC markedly enhanced proliferative responses. In addition, supp lementation of media with IL-1 alpha further enhanced proliferative re sponses and a combination of anti-IL-10 serum and IL-1 alpha was more effective than either agent alone. Only HLA-DR-matched CML cells, but not HLA-DR-mismatched CML cells or matched or mismatched PBMC restimul ated proliferation of IL-2-dependent T cell lines derived from MLTC su pplemented with IL-1 alpha and anti-IL-10 serum. The responding cells under these conditions were predominantly CD4(+) and secreted IL-2, an d interferon gamma; some secreted IL-4, but none secreted IL-10. These data therefore suggest the existence of an HLA-DR-restricted DTH/Th1- type of tumour-specific immunity in CML patients, which may be down-re gulated in vitro by excessive secretion of IL-10 together with depress ed secretion of IL-1.