FAS-independent cell death of HTLV-1-specific clonal cytotoxic T cells upon exposure to autologous HTLV-1-bearing leukemic cells (Meeting abstract).

Important note: Information in this article was accurate in 1995. The state of the art may have changed since the publication date.

FAS-independent cell death of HTLV-1-specific clonal cytotoxic T cells upon exposure to autologous HTLV-1-bearing leukemic cells (Meeting abstract).

Proc Annu Meet Am Soc Clin Oncol; 14:A20 1995. Unique Identifier : AIDSLINE ICDB/95613176
Anderson B; Maeda H; Maeda Y; Lam L; Yang Y; Mitsuya H; NCI, Bethesda, MD 20892

Abstract: HTLV-l-specific clonal cytotoxic T cells (CTL) were generated from a patient with adult T-cell leukemia (ATL). The CTL killed autologous leukemic cells (ALC); however, the coculture resulted in decreased proliferation and death of the CTL. We explored the possible mechanisms of this CTL cell death. Coculture of CTL and irradiated ALC caused a significant degree of CTL DNA fragmentation as demonstrated by DNA filtration assay and extraction of 14C-labeled low molecular weight DNA. This DNA fragmentation was not inhibited by cyclosporin A, dexamethasone, actinomycin D, or cycloheximide suggesting a mechanism independent of the activation state of the CTL. The CTL express functional Fas antigen as demonstrated by fluorescence-activated cell analysis, and cell death, measured by 51Cr-release assay, was found to occur when CTL were incubated with an anti-Fas IgM monoclonal antibody. Preincubation of CTL with myristate acetate phorbol (PMA) virtually completely inhibited the ALC-induced cell death, although it only partially inhibited the anti-Fas IgM-induced CTL death. Also, preincubation of ALC with soluble Fas antigen failed to block the subsequent death of 51Cr-labeled CTL. Finally, when ALC were cocultured with the Fas+ L1210 cell line, no evidence of L1210 cell death was seen. These data suggest that the ALC-induced CTL death is not related to the proposed apoptotic mechanisms requiring cell activation and is not mediated by a Fas-dependent process. The inhibition of this apoptotic process by PMA suggests that an intracellular mechanism leading to the death of the CTL is operating. This phenomenon may suggest a mechanism for the progressive decline of the immune system in patients with ATL.

Keywords: Antibodies, Monoclonal/PHARMACOLOGY Antigens, Surface/IMMUNOLOGY/*PHYSIOLOGY *Apoptosis Cell Communication Cell Death Cells, Cultured Human HTLV-I IgM/PHARMACOLOGY Leukemia-Lymphoma, T-Cell, Acute, HTLV-I-Associated/*IMMUNOLOGY/ *PATHOLOGY T-Lymphocytes, Cytotoxic/*PATHOLOGY Tumor Cells, Cultured ABSTRACT
950930
M9591318

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