Identification and characterization of a membrane-bound cytotoxin of murine cytolytic lymphocytes that is related to tumor necrosis factor/cachectin

Journal Article · Mon May 01 04:00:00 EDT 1989 · Proceedings of the National Academy of Sciences of the United States of America; (USA)

DOI:https://doi.org/10.1073/pnas.86.9.3286· OSTI ID:5161239

Liu, Chauching; Detmers, P A; Jiang, Shibo; Young, J D E ^[1]

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1. Rockefeller Univ., New York, NY (USA)

Cytotoxic T lymphocytes (CTLs) kill their targets by a contact-dependent mechanism. The authors investigated the possibility that the CTL membranes themselves could exert direct cytotoxic activity. Murine CTLs that had been fixed with paraformaldehyde retained a slow cytotoxic activity toward various target cells that are also sensitive to another cytokine, tumor necrosis factor (TNF)/cachectin. This cytotoxic activity was neutralized by antibodies specific for TNF. Membrane fractions obtained from CTLs were cytotoxic to TNF-sensitive targets but not to several TNF-resistant cell lines. Immunoblot analysis revealed a membrane protein band of 50-60 kDa from CTLs that reacts with anti-TNF antibodies. The surface localization of this cytokine was further ascertained by flow cytometry, indirect immunofluorescence, and immunoelectron microscopy studies using TNF-specific antibodies. Radioiodination of CTL surface proteins followed by immunoprecipitation with anti-TNF antibodies confirmed the presence of a TNF-related cytokine in the plasma membranes of CTLs that migrated with an apparent molecular mass of 50-60 kDa under disulfide-reducing conditions. This cytokine can be removed from membranes by treatment with detergents but not with high-salt buffers, suggesting that it may be an integral membrane protein.

• OSTI ID: 5161239
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (USA), Journal Name: Proceedings of the National Academy of Sciences of the United States of America; (USA) Vol. 86:9; ISSN 0027-8424; ISSN PNASA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ADDITIVES
ANIMAL CELLS
ANTIBODIES
ANTIGENS
BETA DECAY RADIOISOTOPES
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY FLUIDS
CELL KILLING
CHEMICAL REACTIONS
CONNECTIVE TISSUE CELLS
DAYS LIVING RADIOISOTOPES
DETERGENTS
DISEASES
ELECTRON CAPTURE RADIOISOTOPES
ELECTRON MICROSCOPY
EMULSIFIERS
GLOBULINS
GROWTH FACTORS
HALOGENATION
IMMUNOGLOBULINS
INTERMEDIATE MASS NUCLEI
IODINATION
IODINE 125
IODINE ISOTOPES
ISOTOPES
LEUKOCYTES
LYMPHOCYTES
LYMPHOKINES
MATERIALS
MEMBRANE PROTEINS
MEMBRANES
MICROSCOPY
MITOGENS
MOLECULAR STRUCTURE
NECROSIS
NEOPLASMS
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
PATHOLOGICAL CHANGES
PROTEINS
RADIOISOTOPES
SOMATIC CELLS
SURFACTANTS
TOXIC MATERIALS
TOXINS
TRANSMISSION ELECTRON MICROSCOPY
WETTING AGENTS