Abstract

The cytolytic mechanism of cloned cytolytic T cells was investigated based on the observation that: (1) cytolytic T cells assemble membrane lesions/polyperforin 1 and polyperforin 2 and (2) that the precursor proteins (perforin) seem to be stored in cytoplasmic granules of T cells. Granules were isolated and tested for their biochemical composition, for their cytolytic activity, and for their ability to form polyperforin complexes. In addition, T-cell clones with different specificities were used for granule isolation to address the question as to whether granule proteins are of clonal origin. Isolated T-cell granules are highly cytolytic for all tumor cells tested. Cytolysis by granules is absolutely dependent on CA ions and is inhibited by Zn?2+?. Granule-mediated lysis is not H2 restricted, and during granule-mediated cytolysis, polyperforins are assembled on target membranes. Granules contain a set of approximately 12 proteins not detectable in other cellular compartments. These cytolytic proteins are identical or very similar in cytologic granules of various cytolytic T-cell clones; and antisera developed to granules from one clone detect granules from other clones. Immunofluorescence studies show a direct role for granules in the cytolytic process. (IS)

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA039201-02
Application #
3177959
Study Section
Experimental Immunology Study Section (EI)
Project Start
1984-06-01
Project End
1986-05-31
Budget Start
1985-06-01
Budget End
1986-05-31
Support Year
2
Fiscal Year
1985
Total Cost
Indirect Cost

  Institution

Name
New York Medical College
Department
Type
Schools of Medicine
DUNS #
City
Valhalla
State
NY
Country
United States
Zip Code
10595

  Publications

McCormack, Ryan M; Lyapichev, Kirill; Olsson, Melissa L et al. (2015) Enteric pathogens deploy cell cycle inhibiting factors to block the bactericidal activity of Perforin-2. Elife 4:
McCormack, Ryan M; de Armas, Lesley R; Shiratsuchi, Motoaki et al. (2015) Perforin-2 is essential for intracellular defense of parenchymal cells and phagocytes against pathogenic bacteria. Elife 4:
McCormack, Ryan; de Armas, Lesley R; Shiratsuchi, Motoaki et al. (2013) Inhibition of intracellular bacterial replication in fibroblasts is dependent on the perforin-like protein (perforin-2) encoded by macrophage-expressed gene 1. J Innate Immun 5:185-94
Fields, K A; McCormack, R; de Armas, L R et al. (2013) Perforin-2 restricts growth of Chlamydia trachomatis in macrophages. Infect Immun 81:3045-54
McCormack, Ryan; de Armas, Lesley; Shiratsuchi, Motoaki et al. (2013) Killing machines: three pore-forming proteins of the immune system. Immunol Res 57:268-78
Fang, Lei; Adkins, Becky; Deyev, Vadim et al. (2008) Essential role of TNF receptor superfamily 25 (TNFRSF25) in the development of allergic lung inflammation. J Exp Med 205:1037-48
Xiao, Yanping; Motomura, Seiichi; Podack, Eckhard R (2008) APRIL (TNFSF13) regulates collagen-induced arthritis, IL-17 production and Th2 response. Eur J Immunol 38:3450-8
Oizumi, Satoshi; Deyev, Vadim; Yamazaki, Koichi et al. (2008) Surmounting tumor-induced immune suppression by frequent vaccination or immunization in the absence of B cells. J Immunother 31:394-401
Podack, Eckhard R; Deyev, Vadim; Shiratsuchi, Motoaki (2007) Pore formers of the immune system. Adv Exp Med Biol 598:325-41
Oizumi, Satoshi; Strbo, Natasa; Pahwa, Savita et al. (2007) Molecular and cellular requirements for enhanced antigen cross-presentation to CD8 cytotoxic T lymphocytes. J Immunol 179:2310-7

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