Cellular immune responses to autologous chronic myelogenous leukaemia cells in vitro.
Using a modification of the autologous mixed lymphocyte/tumour cell culture (MLTC), it is demonstrated here that lymphocytes from chronic-phase myelogenous leukaemia (CML) patients (n = 58), but not from their HLA-identical siblings, proliferated upon coculture with autologous tumour cells. However, in most cases, the level of proliferation measured was low (stimulation index < 3, n = 37). This was most likely related to the amount of interleukin-10 (IL-10) released into the culture medium by the CML cells, because addition of neutralizing anti_IL-10 serum to MLTC markedly enhanced proliferative responses. In addition, supplementation of media with IL-1 alpha further enhanced proliferative responses 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 restimulated proliferation of IL-2-dependent T cell lines derived from MTLC supplemented with IL-1 alpha and anti-IL-10 serum. The responding cells under these conditions were predominantly CD4+ and secreted IL-2, and 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-regulated in vitro by excessive secretion of IL-10 together with depressed secretion of IL-1.
Pawelec
G
G
Second Department of Internal Medicine, Tübingen University Medical School, Germany.
Rehbein
A
A
Schlotz
E
E
da Silva
P
P
D002478:Cells, Cultured; D003561:Cytarabine / Q000494:pharmacology; D016207:Cytokines / Q000096:biosynthesis; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology; D007375:Interleukin-1 / Q000096:biosynthesis / Q000276:immunology; D016753:Interleukin-10 / Q000096:biosynthesis / Q000276:immunology; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000097:blood / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism
D016207:Cytokines; D000949:Histocompatibility Antigens Class II; D007375:Interleukin-1; D003561:Cytarabine; D016753:Interleukin-10