Cytotoxic T‐Lymphocytes How Do They Function?

Berke, Gideon

doi:10.1111/j.1600-065x.1983.tb01071.x

Cited by 114 publications

(37 citation statements)

References 112 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The lack of effect of serum and serum HDL and LDL on membrane-bound PFP suggests that once PFP has bound to bilayers, lysis would proceed to completion in the presence of a calcium and neutral pH environment even when the killer cells are no longer in close attachment with the targets. This possibility would be consistent with previous reports (28,29) describing a self-programmed, Ca"-dependent, but killer cellindependent stage in lymphocyte-mediated killing which occurs after contact and dissolution of the lymphocyte from the target .…”

Section: Discussionsupporting

confidence: 81%

Dissociation of membrane binding and lytic activities of the lymphocyte pore-forming protein (perforin).

Young¹,

Damiano²,

Dinome³

et al. 1987

The Journal of Experimental Medicine

View full text Add to dashboard Cite

Granules isolated from CTL and NK cells contain a cytolytic pore-forming protein (PFP/perforin). At low temperatures (on ice), PFP binds to erythrocyte membranes without producing hemolysis. Hemolysis occurs when the PFP-bound erythrocytes are warmed up to 37 degrees C, which defines a temperature-dependent, lytic (pore-formation) step distinct from the membrane-binding event. Ca2+ and neutral pH are required for both membrane binding and pore formation by PFP. Serum, LDL, HDL, and heparin inhibit the hemolytic activity of PFP by blocking its binding to lipid membranes. Lysis by PFP that has bound to erythrocyte membranes is no longer susceptible to the effect of these inhibitors. The hemolytic activities associated with intact granules and solubilized PFP show different requirements for Ca2+ and pH, indicating that cytolysis produced by isolated granules may involve an additional step, possibly fusion of granules with membranes. It is suggested that three distinct Ca2+- and pH-dependent events may be involved during cell killing by CTL and NK cells: fusion of cytoplasmic granules of effector cells with their plasma membrane, releasing PFP from cells; binding of the released PFP to target membranes; and insertion of monomers and the subsequent formation of lytic pores in the target membrane. The serum-mediated inhibition of membrane binding by PFP could prevent the accidental injury of bystander cells by cell-released PFP, but would allow cytolysis to proceed to completion once PFP has bound to the target membrane.

show abstract

Section: Discussionsupporting

confidence: 81%

Dissociation of membrane binding and lytic activities of the lymphocyte pore-forming protein (perforin).

Young¹,

Damiano²,

Dinome³

et al. 1987

The Journal of Experimental Medicine

View full text Add to dashboard Cite

show abstract

“…Undoubtedly these clones will provide very useful markers to study the molecular events involved in the regulation of gene expression during T-cell ontogeny. Moreover, identification of the proteins they encode may provide clues to how these specialized end-stage cells function in target-cell lysis (18).…”

mentioning

confidence: 99%

Cloning of two genes that are specifically expressed in activated cytotoxic T lymphocytes.

Lobe¹,

Havele²,

Bleackley³

1986

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

The intracellular events leading to cytotoxic T-lymphocyte (CTL) activation and the molecular mechanism of target-cell lysis remain largely unknown. Differential hybridization analysis of a library constructed from a cloned CTL line was used to identify sequences specifically expressed in CTL. Two clones were selected for extensive analysis. No evidence for expression of their mRNAs was found in helper T-cell lines, thymocytes, lipopolysaccharide-activated B cells, interferon-treated natural killer cells, and a number of nonlymphoid cells. Blot-hybridization analysis of CTL mRNA revealed that one clone detected a single 900-nucleotide mRNA, whereas the other hybridized to two mRNAs of 900 and 1200 nucleotides, respectively. The maximum expression of these mRNAs precedes the peak of cytotoxicity in an in vitro allogeneic or mitogen-induced cytotoxic response by 24 hr; thus, they both fulfill the primary prerequisite for genes encoding proteins that are important in either CTL activation or in the lytic process itself.

show abstract

“…The processes by which cytolytic lymphocytes destroy such cells is not completely understood. Current concepts view cytolysis as a multistep physiologic process minimally involving initial weak attachment of the lymphocyte to the target cell, specific recognition, transmembrane signaling that strengthens attachment, further bidirectional signaling events that ultimately program the target cell for destruction, lysis of the target cell, and recycling of the effector cell to another target (for reviews see references [1][2][3][4][5]. These processes are likely mediated by receptor-ligand interactions that may vary somewhat depending on the particular combination of effector and target cell and/or the cytolytic pathway used (5,6).…”

mentioning

confidence: 99%

A novel ligand in lymphocyte-mediated cytotoxicity: expression of the beta subunit of H+ transporting ATP synthase on the surface of tumor cell lines.

Das

Mondragon

Sadeghian

et al. 1994

The Journal of Experimental Medicine

126

109

View full text Add to dashboard Cite

SummaryExtracellular adenosine triphosphate (eATP) has been suggested to play a role in lymphocyteinduced tumor destruction. We now provide evidence that a protein responsible for ATP synthesis in mitochondria may also play a physiologic role in major histocompatibility complex-independent, lymphocyte-mediated cytotoxicity. A 51.5-kD protein (p51.5) beating structural and immunologic characteristics of the B subunit of H + transporting ATP synthase (E.C. 3.6.1.34, B-H +ATPase, published molecular mass of 51.6 kD) was detected on the plasma membrane of three different human tumor cell lines studied. NH2-terminal amino acid sequence analysis of purified p51.5 from K562 tumor cells revealed 100% homology of 16 residues identified in the first 21 positions to the known sequence of human mitochondrial B-H § ATPase. Antibody directed against a 2l-iner peptide in the ATP binding region of B-H+ATPase (anti-B) reacted with only one band on Western blots of whole tumor extracts and tumor membrane extracts suggesting that the antiserum reacts with a single species of protein. Anti-B reacted with the cell membranes of tumor ceils as determined by fluorescence-activated flow cytometry and immunoprecipitated a 51.5-kD protein from surface-labeled neoplastic cells (but not human erythrocytes and lymphocytes). Purified p51.5 bound to human lymphocytes and inhibited natural killer (NK) cell-mediated cytotoxicity. Furthermore, anti-B treatment of the K562 and A549 tumor cell lines inhibited NK (by >95%) and interleukin 2-activated killer (LAK) cell (by 75%) cytotoxicity, respectively. Soluble p51.5 upon binding to lymphocytes retained its reactivity to anti-B suggesting that the ATP binding domain and the lymphocyte-receptor binding domain reside in distinct regions of the ligand. These results suggest that B-H +ATPase or a nearly identical molecule is an important ligand in the effector phase (rather than the recognition phase) of a cytolytic pathway used by naive NK and LAK cells.

show abstract

Cytotoxic T‐Lymphocytes How Do They Function?

Cited by 114 publications

References 112 publications

Dissociation of membrane binding and lytic activities of the lymphocyte pore-forming protein (perforin).

Dissociation of membrane binding and lytic activities of the lymphocyte pore-forming protein (perforin).

Cloning of two genes that are specifically expressed in activated cytotoxic T lymphocytes.

A novel ligand in lymphocyte-mediated cytotoxicity: expression of the beta subunit of H+ transporting ATP synthase on the surface of tumor cell lines.

Contact Info

Product

Resources

About