Search PubMed⌕ Search

Biomedical subjects

E Martz

Publications and source records attributed to E Martz.

52 records · Page 3Linked to original sources
PubMed1976

Multiple target cell killing by the cytolytic T lymphocyte and the mechanism of cytotoxicity.

Previous reports have shown that one cytolytic T lymphocyte (CTL) can kill more than one allogeneic target cell, but have not established whether after its action on one or more target cells, each CTL can attack a second set of target cells at a later time. The experiments described here show that one CTL can kill more than six target cells, and they suggest that CTL can do this sequentially in time. Hence, the small number of specifically sensitized lymphocytes found in rejecting grafts could play an important role. Moreover, sequential killing would imply that CTL are not harmed during their interaction with specific target cells. If killing were effected by secretion of a nonspecific toxin, the killer cell would then have evolved some device for resisting its own toxin in order to survive. Whether or not this is the case has not yet been fully resolved.

Animals↗
PubMed1976

Early steps in specific tumor cell lysis by sensitized mouse T lymphocytes. II. Electrolyte permeability increase in the target cell membrane concomitant with programming for lysis.

In a previous study of the mechanism of specific target cell lysis by alloimmune cytolytic T lymphocytes (CTL), we established that the target cell becomes irreversibly programmed to lyse within a few minutes after contact with the CTL. We here show that at each point in time, the level of specific release of the potassium analog, 86Rb equals the percentage of target cells which have been programmed to lyse. It is also shown that specific release of 86Rb is more rapid than that of a small metabolite of similar weight, 14C-nicotinamide, which in turn is specifically released more rapidly than 51Cr. Thus, an electrolyte-permeable lesion is produced in the target cell membrane within minutes of contact with the CTL. Since measurements of 86Rb release, unlike measurements of programming for lysis, do not involve exposure of the cells to EDTA and vigorous shearing forces, the present observations corroborate and extend, by an independent and gentler method, our previous conclusion that the CTL effects crucial and irreversible changes in the target cell within minutes after contact. The present results are consistent with the possibility that the first, and perhaps the only damage administered directly by the CTL is a membrane lesion permeable to electrolytes and possibly to small molecules.

Animals↗
PubMed1975

Early steps in specific tumor cell lysis by sensitized mouse T lymphocytes. I. Resolution and characterization.

Addition of high molecular weight dextran to culture medium prevents the initiation of T lymphocyte-mediated killing by holding the cytolytic T lymphocytes (CTL) and target cells in suspension and preventing intercellular contact. Suspension in 10% dextran was used to interrupt the ongoing formation of adhesions between CTL and target cells already in contact in a centrifuged pellet. The results demonstrate that 1) firm adhesions form between CTL and target cells within 1 min at 37 degrees C; 2) once formed, these adhesions are stable at low temperature and are resistant to mechanical shearing forces; 3) these adhesions can be disrupted by EDTA; 4) immediately after the adhesions form, separation of the CTL from the target cells prevents lysis of the latter; 5) after incubation of targets adhering to CTL for an additional 6 min at 37 degrees C, removal of the CTL no longer prevents target cell lysis. Thus, target cells become "programmed" for subsequent lysis within a few minutes after contact with CTL, after which lysis occurs during the next several hours without further participation of the effector cell. At 15 degrees C, adhesions form 1/17 as fast as at 37 degrees C. Programming of target cells for lysis occurs 1/76 as fast at 15 degrees C as at 37 degrees C. Thus, the programming for lysis step is about 4-fold more temperature dependent than the adhesion step. In addition to being detected by subsequent target cell lysis in 10% dextran, the adhering cell clusters can be counted with low power microscopy. This permitted verification that EDTA separates the clusters after programming for lysis is complete. Moreover, the great majority of the clusters seen at 37 degrees C are antigen-specific. Knowledge of the cluster size distribution and the subsequent level of lysis permits the deduction that not less than 6% of the sensitized peritoneal cell populations used were CTL.

Animals↗
PubMed1974

Interruption of the sequential release of small and large molecules from tumor cells by low temperature during cytolysis mediated by immune T-cells or complement.

Specific lysis of tumor cells by thymus-derived lymphocytes from alloimmunized mice (T-effector specific lysis) was studied with target cells labeled with isotopes attached to both small ((14)C-labeled nicotinamide) and large ((51)Cr-labeled) molecules. The results confirm and extend previous reports that target cells release small molecules considerably earlier than large molecules during T-effector specific lysis. After interruption of T-effector specific lysis by specific antibody and complement directed against the killer cells, or by ethylenediaminetetraacetic acid, release of both isotopes continued, eventually reaching identical levels of specific release, the value of which represents the fraction of the target cell population which had been committed to die at the time these treatments were applied. On the other hand, release of both isotopes during T-effector specific lysis stops immediately when the cultures are cooled to 0 degrees . Thus, while ethylenediaminetetraacetic acid or specific complement-mediated lysis of the killer cells merely prevents the initiation of any new damage to target cells, cooling to 0 degrees also stops the lytic process in already-damaged target cells. The colloid osmotic phase of target cell lysis induced by specific antibody and complement was similarly stopped at 0 degrees in tumor cells, but not in erythrocytes. Thus, in tumor target cells, both T-effector specific lysis and complement cause a sequential release of progressively larger molecules which can be immediately stopped at any point by cooling to 0 degrees .

Animals↗