Soluble factors, including TNF alpha, secreted by human T cells are both cytotoxic and cytostatic for medulloblastoma cells.
We studied the effect of the treatment of a medulloblastoma cell line by human T cells derived soluble factors. Medulloblastoma is one of the more common aggressive solid neoplasms in children for which there is no adequate therapy. Cell lines established from such tumours may be helpful to test the effect of various molecules on cell proliferation. Previous studies have suggested that T cell-derived factors may be toxic for the medulloblastoma cell line Dev. Cytokines were thought to mediate this effect. In this paper, we described changes in morphology, survival and cell cycle induced in Dev cells cocultured with human T cell lines chronically infected with a retrovirus (HTLV-I) and known to secrete high level of cytokines TNF alpha, IL1alpha and IL6. Such cocultures resulted in the death of a part of Dev cells and in decreased proliferation of surviving cells, associated with morphological changes and increase in vimentin expression. Treatment with conditioned medium from infected Dev cells, containing virus induced cytokines, triggered the same effect. Reduction of these effects by TNF alpha deprivation of conditioned medium suggested that this cytokine may be implicated. Direct treatment of Dev cells with recombinant cytokines indicated that TNF alpha, but not IL1 or IL6, is associated with Dev cell alterations. TNF alpha was shown to induce the death of Dev cells by an apoptotic pathway. Furthermore, TNF alpha had a bimodal effect on the cell cycle of surviving Dev cells. These differential effects of such cytokines on medulloblastoma cells could be therefore of interest for immunotherapy of these tumours.
Dufay
N
N
INSERM U433, Hôpital Neurologique et Neurochirurgical, BP Lyon Montchat, France.
Reboul
A
A
Touraine-Moulin
F
F
Belin
M F
MF
Giraudon
P
P
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000528:radiation effects; D002453:Cell Cycle / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002528:Cerebellar Neoplasms / Q000276:immunology; D018920:Coculture Techniques; D017077:Culture Media, Conditioned; D003599:Cytoskeleton / Q000187:drug effects / Q000648:ultrastructure; D003603:Cytotoxins / Q000096:biosynthesis / Q000633:toxicity*; D005720:Gamma Rays; D006801:Humans; D020287:In Situ Nick-End Labeling; D007375:Interleukin-1 / Q000096:biosynthesis / Q000633:toxicity*; D015850:Interleukin-6 / Q000096:biosynthesis / Q000633:toxicity*; D007700:Kinetics; D008527:Medulloblastoma / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000528:radiation effects; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000633:toxicity*
D017077:Culture Media, Conditioned; D003603:Cytotoxins; D007375:Interleukin-1; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha