SEARCH · PubMed Health

Results for “effector”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 37 records · Page 2Linked to original sources

PubMed1975

Specific and nonspecific antitumor immunity. II. Macrophage-mediated nonspecific effector activity induced by BCG and similar agents.

The recently described inhibition of DNA synthesis (IDS) assay, which measures antitumor effector (E) cell function by the quantitation of decreases in tritiated thymidine incorporation of target tumor cells, was used to analyze the nonspecific effector activity of peritoneal exudate cells (PEC) from mice infected intraperitoneally with BCG. These PEC could inhibit growth of and then kill all tumor target (effector to target) cells tested at E/T ratios as low as 1:1. This activity was not due to alterations in media, nor could any activity be shown for cell-free supernatants prepared from active cells. The principal cell type mediating this effector function was the "activated" macrophage-no activity was found in lymphoid or polymorphonuclear leukocytes. Direct effector to target contact was necessary for the cytotoxic reaction. The time course of these effects and comparative 51Cr release data were reported. The removal of the adherent nonspecific effectors from PEC of mice immunized to both BCG and a specific syngeneic tumor revealed a specific cytotoxicity of the remaining lymphoid cells. These results indicated that nonspecific effector activity by "activated" macrophages induced by BCG infection could be a potent antitumor mechanism, at least in vitro, and the IDS assay provided an accurate, reproducible, and quantitative method for measurement of the function of such E cells.

Animals↗

PubMed1979

Correlation between effector lymphocytes in natural and antibody-mediated cytotoxicity.

Human sera enhanced spontaneous cell-mediated cytotoxicity (SCMC), while anti-IgG (Fab') 2 treatment decreased this cytotoxic activity of human lymphocytes for an in vitro growing cell line (K--562). Trypsin treatment of the effector cells considerably decreased the cytotoxic potential. However, a significant cytotoxic activity could always be found in serum-free medium. While these findings suggest the involvement of antibodies in the SCMC, they also reflect the existence of serum-indpendent (sui generis) SCMC activity of lymphocytes. Removal of SCMC of Fc receptor bearing effector cells was performed by target cell adherence (rosetting). Separation of the target cell-bound lymphocytes was done by centrifugation on special Ficoll gradient. The depletion of SCMC effector cells resulted in a 62% reduction of SCMC and in a 39% reduction of ADCC. On the other hand, removal of Fc bearing effector cells showed a similar reduction in both ADCC (66%) and SCMC (78%). Our results suggest that SCMC represents a complex activity, arising partly from the interactions of certain serum-derived or lymphocytes surface-bound antibodies and partly from a spontaneous cytotoxic function of the effector cells. It is possible that the effector cells involved in both SCMC and ADCC derive from the same lymphocyte population and the differences are due mainly to the lower number of SCMC effector cells.

Animals↗

PubMed2026

Integrated Functional Characterization of Hemileia vastatrix Effector Candidates Reveals Coordinated Immune Suppression, Sequential Deployment and Compartment-Specific Targeting.

Coffee leaf rust, caused by the obligate biotrophic fungus Hemileia vastatrix, remains the most destructive disease of coffee worldwide. Although genomic and transcriptomic studies have identified a large number of candidate effectors, experimental evidence supporting their biological roles during infection remains limited. Here, we integrated functional assays, temporal expression profiling during coffee infection and subcellular localization analyses to investigate the biological properties of 44 H. vastatrix effector candidates (HvECs). Using the Pseudomonas fluorescens EtHAn effector delivery system in Nicotiana benthamiana, 15 HvECs consistently suppressed pattern-triggered immunity (PTI), indicating that immune suppression is a widespread property among the H. vastatrix effector repertoire, as assessed in this heterologous system. Five HvECs also attenuated AvrB-triggered effector-triggered immunity (ETI), and three suppressed both PTI and ETI, suggesting that a subset of HvECs targets conserved regulatory nodes shared by these interconnected immune pathways. Temporal expression profiling revealed sequential deployment of HvECs throughout infection, with distinct subsets predominating during pre-biotrophic development, host penetration or biotrophic colonization, consistent with stage-specific functions during fungal pathogenesis. Subcellular localization analyses further showed that HvECs preferentially accumulated in the nucleus or chloroplasts, compartments known as central hubs of plant immune regulation. This study provides the most comprehensive functional characterization of H. vastatrix effector candidates to date, establishes a biologically informed framework for prioritizing candidates for future identification of avirulence determinants recognized by SH resistance genes, and advances our understanding of how the coffee rust fungus orchestrates immune suppression across time and cellular space during pathogenesis.

Nicotiana↗

PubMed1978

H-2-restricted cytotoxic effectors generated in vitro by the addition of trinitrophenyl-conjugated soluble proteins.

Murine spleen cells from normal donors were cultured in vitro with trinitrobenzene sulfonate (TNBS)-conjugated soluble proteins, i.e., bovine gamma globulin (TNP-BGG) or bovine serum albumin (TNP-BSA). Addition of 100 mug of any of these TNP-proteins to the spleen cell cultures led to the generation of cytotoxic T-cell effectors which were H-2-restricted and TNP- specific. The lytic potential of such effectors was comparable to that generated by sensitization with TNBS-modified syngeneic cells, and was restricted to haplotypes shared at the K or K plus I-A, or the D regions of the H-2 complex. Greater effecter cell activity was generated by addition of TNP-BGG against TNBS-modified targets which shared K plus I-A than against modified targets which shared the D region with the responding cells, which suggests that the same immune response genes are involved when the response is generated by the addition of TNP-conjugated soluble proteins or of TNBS- modified cells. H-2-restricted, TNP-specific effecter cells were generated by culturing mouse spleen cells with syngeneic cells which had been preincubated with TNP- BGG or TNP-BSA for 1.5 h. The addition of unconjugated soluble proteins to the cultures did not result in cytotoxic effectors detectable on H-2-matched targets, whether the targets were prepared by modification with TNBS, or by incubation with either the unconjugated or TNP-conjugated proteins. Depletion of phagocytic cells in the tumor preparation by Sephadex G-10 column fractionation before incubation with TNP-BSA had no effect on their lysis by the relevant effector cells. Immunofluorescent staining of tumor target cells with anti-TNP antibodies indicated that TNP could be detected on the tumor cells within 10 rain of incubation with TNP-BSA. The cytotoxic response generated by addition of the TNP-proteins to spleen cell cultures was found to be T-cell dependent at the effector phase, as shown by the sensitivity of the lytic phase to absorbed RAMB and complement. Furthermore, the response did not appear to be attributable to antibody-dependent cellular cytotoxicity. Three mechanisms were considered which could account for the generation of H-2-restricted, TNP-specific, cytotoxic T-cell effectors by the addition of soluble TNP-proteins. These include covalent linkage of activated TNP groups from the soluble proteins to cell surface components, macrophage processing of the soluble conjugates and presentation to the responding lymphocytes in association with H-2-coded self structures, or hydrophobic interaction of the TNP-proteins to cell surfaces. Results obtained from sodium dodecyl sulfate gel patterns indicating that cell-bound TNP was still linked to BSA, and the observation that phagocytic-depleted cells could interact with the soluble TNP-proteins and function as H-2-restricted targets, appear not to favor the first two proposed mechanisms.

Animals↗

PubMed1975

Antibody-dependent cell-mediated cytotoxicity: heterogeneity of effector cells in human peripheral blood.

We have compared antibody-dependent cell-mediated cytotoxicity (ADCMC) of human peripheral blood leukocytes (PBL) in three model systems. target cells were 51Cr-labeled mouse mastocytoma cells, chicken erythrocytes (CRBC), and human erythrocytes (HRBC) coated with appropriate heterologous or isologous antisera. Effector cells were characterized on the basis of their adherence, phagocytosis, radiosensitivity, and sedimentation velocity(s) at 1 g. In predominantly mononuclear (Ficoll-Isopaque-purified) PBL preparations (MPBL) HRBC were lysed by an adherent, phagocytic population of cells that was markedly radio-resistant. Sedimentation velocity analysis further established that these effector cells were restricted to rapidly sedimenting fractions (s greater than 4.5 mm/hr). On the other hand, mastocytoma cells were lysed by a population of MPBL that was nonadherent, nonphagocytic, and relatively radiosensitive. These cells mainly restricted to slowly sedimenting fractions (s greater than 4.5 mm/hr) following 1 g velocity sedimentation. CRBC appeared to be susceptible to lysis by both types of mononuclear effector cell. In some experiments, enriched populations of polymorphonuclear leukocytes (PMN) were isolated. These cells were found to lyse both HRBC and CRBC very efficiently, whereas mastocytoma cells were lysed very little if at all by the same effector populations. Taken together, these results suggest that antibody-coated mastocytoma cells are lysed uniquely by effector cells in human peripheral blood with the physical properties of lymphocytes, whereas antibody-coated HRBC are lysed by both monocytes and PMN, but not by lymphocytes. Antibody-coated CRBC would appear to be lysed by all of the three effector cell types tested.

Animals↗

PubMed1976

Secondary cytotoxic cell response to lymphocytic choriomeningitis virus. I. Kinetics of induction in vitro and yields of effector cells.

Secondary (memory) cell-mediated cytotoxic responses in lymphoid cells from CBA/H mice pre-primed with lymphocytic choriomeningitis virus (LCM) 5-7 weeks previously were induced by culturing these cells in vitro with syngeneic, infected peritoneal cells at 37 degrees for periods of up to 5 days. Cytotoxic effectors were assayed against LCM infected, H-2 compatible target cells in a 51Cr release assay. Response was greater with a higher ratio (1:10) of infected peritoneal cells:pre-primed cells than with lower ratios (e.g. 1:250). Separating responders from infected cells by a 450 mmum nucleopore membrane (coarse enough to allow passage of virus particles) still permitted induction of a secondary response whilst interposition of a 50 mmum nucleopore membrane (which apparently prevented transit of virus particles) virtually abolished the secondary response. Removal of phagocytic cells from responders prior to setting up memory cultures greatly reduced responders' capacity to be induced. Fixed, infected stimulators still induced strong secondary responses. Secondary response was maximal with spleen cells, peripheral blood lymphocytes, or pooled iliac and lumbar lymph node cells. Thymocytes responded less well, whilst mesenteric lymphoid cells and peritoneal cells gave minimal responses. Effector cells from memory cultures killed targets with single-hit kinetics and a rectilinear log effectors: log targets lysed relation held. Memory spleen cells developed increasing cytolytic activity from 2 to 5 days in culture. Memory-generated effectors were markedly potent by day 5, e.g. giving 70 per cent specific release at a killer:target ratio of 0-8:1. Peak DNA synthesis occurred on day 4. We conclude that memory effectors as a population differ in kinetics and potency from effectors obtained by primary viral challenge in the mouse.

Animals↗

PubMed1977

ADCC effector cells in a murine adenocarcinoma. I. Evidence for blood-borne bone-marrow-derived monocytes.

The origin and identity of effector cells for anti-body-dependent cell-mediated cytotoxicity and/or growth inhibition (ADCC) found in the murine mammary adenocarcinoma T1699 were investigated. Non-phagocytic, non-adherent ADCC effector cells were identified in bone marrow, peripheral blood and the host fraction of the tumor but not from lymphoid organs. These cells were shown to be distinct from the specific growth-inhibitory "armed monocytes" also identified in situ. The ADCC effector cells possess low levels of EA Fc receptors and appear to express a macrophage-associated antigen. Both the bone-marrow and the in situ effector cells became phagocytic after overnight incubation, providing further evidence for the monocyte-macrophage lineage of these cells. The results suggest that bone-marrow-derived blood-borne monocytes are the principal ADCC effector cells localizing in the mammary adenocarcinoma T1699. The parallels between tumor-induced immunity and cellular resistance to infectious agents involving hypersensitivity reactions and blood-borne monocytes are discussed.

Adenocarcinoma↗

PubMed1978

Studies of effector cell, antibody, and target cell interactions in natural cell-mediated cytotoxicity.

IgG antibodies bound to effector cells through Fc receptors were observed to determine the specificity of natural cell-mediated cytotoxicity (NCMC) against cultured target cells. When effector lymphocytes were isolated from the peripheral blood of most individuals, they already possessed natural antibodies specific for antigens on cultured cells. Since they lacked IgG antibodies specific for antigens on sheep red blood cell (SRBC) targets, natural cytotoxicity against SRBC was almost non-existent. Effector cells incubated in IgG anti-SRBC became specifically cytotoxic to SRBC. In the process, NCMC and antibody-dependent cell-mediated cytotoxicity was diminished, indicating that arming with anti-SRBC replaced natural antibodies and occupied Fc receptors on effector cells. Thus, treating effector cells with serum may result in increased or decreased cytotoxicity depending upon the specificity of antibodies within the serum. This type of modulation of NCMC occurs at the interaction between antibody Fc and Fc receptors and can explain blocking and unblocking.

Animals↗

PubMed1975

Glucocerebrosidase: stoichiometry of association between effector and catalytic proteins.

1. The effector and catalytic proteins of glucocerebrosidase associated in the presence of acidic phospholipid to give active enzyme. 2. At optimum concentrations of acidic phospholipid (about 0.15 mM), the association reached equilibrium instantaneously. 3. From the experimental data, a tentative model of the association was deduced. This involved a two-step complex formation. When the effector concentration was limiting, a simple binary complex was formed between one molecule each of effector and catalytic proteins; the reaction proceeded rapidly to completion. When the effector was in excess, a ternary complex was formed by the addition of another molecule of effector; this reaction did not go to completion and was characterised by a finite equilibrium constant. 4. The experimental data were curve fitted to an equation derived from the model

Cell Membrane↗

PubMed1977

Binding of allosteric effectors to carbamyl-phosphate synthetase from Escherichia coli.

The binding of ornithine and inosine 5'-monophosphate (IMP), positive allosteric effectors, and of uridine 5'-monophosphate (UMP), a negative allosteric effector, to carbamyl-phosphate synthetase from Escherichia coli was studied by the technique of equilibrium dialysis. The monomeric form of the enzyme has one binding site for each of the three allosteric ligands. The binding of UMP is inhibited by ornithine, IMP, MgATP, and ammonia (also a positive allosteric effector). Bicarbonate, L-glutamine, and adenosine 5'-triphosphate (ATP) (Mg2+ absent) had no effect on the binding of UMP. The affinity of the enzyme for UMP was increased if phosphate buffer was replaced by 2-amino-2-hydroxymethyl-1,3-propanediol (Tris) buffer. The binding of ornithine was inhibited by UMP and ammonia, enhanced by MgATP, MgADP, and IMP, and not affected by bicarbonate, L-glutamine, or ATP (Mg2+ absent). Ornithine and ammonia probably bind to the same site on the enzyme. The binding of IMP is facilitated by ornithine and ammonia, but is inhibited by MgATP or ATP, indicating that adenine nucleotides can also bind to the IMP binding site. The results of these binding studies are consistent with a scheme previously proposed in which the allosteric effectors function by stabilizing one or the other of two different conformational states of the enzyme which are in equilibrium with each other (Anderson, P.M., and Marvin, S.V. (1970), Biochemistry 9, 171). According to this scheme, binding of the substrate MgATP is greatly facilitated when the enzyme exists in the conformational state stabilized by the positive allosteric effectors.

Allosteric Regulation↗

PubMed1975

On the role of the H-2 histocompatibility complex in determining the specificity of cytotoxic effector cells sensitized against syngeneic trinitrophenyl-modified targets.

Spleen cells cultured with syngeneic trinitrophenyl (TNP)-modified stimulator cells display a cytotoxic effect against syngeneic TNP-modified targets, but not against modified targets from unrelated H-2 haplotypes. Targets that share the K and I region of the H-2 complex with the stimulator (or effector) cell are lysed to the same extent as the specific targets, while targets that share the I region only are not. When only the D region is shared, a weak cytotoxic effect is observed. Therefore, the stimulator (or effector) and target cell must share the K or D but not the I region of the H-2 complex in order for optimal cytotoxicity to occur. Spleen cells sensitized to irradiated TNP-modified H-2-allogeneic cells are cytotoxic to these specific cells. Coculture of F1 hybrid cells with irradiated TNP-modified parental cells result in a cytotoxic effect against only those specific parental cells and not TNP-modified cells from the other parent. The cytotoxic effect of the F1 effector cells in the cell-mediated lympholysis test is blocked by the addition of unlabeled TNP-modified targets that are H-2 syngeneic with the sensitizing parental strain, but not H-2 syngeneic with the other parental strain. These data demonstrate that the specificity of the effector cell in this syngeneic cytotoxicity system is directed against altered self H-2-controlled-gene products, rather than a requirement for sharing of histocompatibility genes between effector and target cell in order for lysis to occur. The role of H-2 antigens in determining the sensitivity of a target cell to T-cell-mediated lysis is discussed.

Animals↗

PubMed1977

Specificity of cytotoxic effector cells directed against trinitrobenzene sulfonate-modified syngeneic cells. Failure to recognize cell surface-bound trinitrophenyl dextran.

Mouse splenic lymphocytes and lymphoid tumor cells were modified with the trinitrophenyl (TNP) group either by treatment with trinitrobenzene sulfonate (TNBS) (which covalently modifies cell surface proteins) or with TNP stearoyl dextran (TSD) (which binds to the cell by noncovalent forces). These cell preparations were compared for their ability to: (a) sensitive syngeneic splenic lymphocytes leading to the generation of cytotoxic effector cells; (b) serve as lysable targets in a 4-h(51)Cr- release assay for effector cells generated in (a); and (c) act as blocking cells in the lysis of TNBS-medified targets lysed by TNP self effector cells generated in (a). In none of these three experimental systems did TSD-medified syngeneic spleen or H-2-matched tumor cells act either as a sensitizing immunogen or as a target antigen, despite the demonstration that quantitatively equivalent mounts of TNP were exposed on the cell surface in the TNBS- and TSD-modified cells. In contrast, TNBS-modified spleen cells sensitized syngeneic lymphocytes to generate effectors against TNBS-modified syageneic targets. Furthermore, TNBS- modified, H-2-matched cells served as specific lysable targets and as inhibiting cells for such effectors. These results indicate that the manner in which TNP is associated with the cell surface is important in the immunogenicity and antigenicity of hapten-modified syngeneic stimulating cells in generating H-2-associated cell-mediated lympholysis (CML) reactions. These findings raise the possibility that a covalent or at least a stable linkage with cell surface proteins (possibly H-2- controlled products) is important for immunological function. Furthermore, these observations do not favor the dual receptor model for H-2-restricted syngeneic CML if it is assumed in such a model that one receptor is specific for the TNP moiety and the second for unmodified self major histocompatibility products.

Animals↗

PubMed1976

The distribution of effector cells for antibody-dependent cytotoxicity is species dependent.

Murine lymphoma cells were lysed by using either an allogeneic or a xenogeneic (rat) antiserum and antibody-dependent effectors from mice and rats. It was found that murine spleens were poorly antibody-dependent effectors against this target. The peritoneal cavities of mice were a good source of effectors. In rats, the spleen contained effectors, whereas adherent cells from the peritoneal cavity were comparatively ineffective. Cells from both rat and murine spleens lysed sheep erythrocytes in conjunction with an appropriate antiserum. The data emphasize that there is a difference in the antibody-dependent lysis of erythrocytes compared to nucleated mammalian cells. They also demonstrate that the distribution of antibody-dependent effectors is species dependent.

Animals↗

PubMed1976

Lymphocyte-mediated cytotoxicity against tumor cells specificity and characterization of concanavalin A-activated cytotoxic effector lymphocytes.

The selective T cell mitogen Con A was found to induce cytotoxic effectorlymphocytes after in vivo or in vitro treatment. The effector cells exhibited immunologic specificity when tested against tumor cells, killing targets only across H-2 histocompatibility barriers. Thus, Con A caused a polyclonal T cell activation, resulting in the appearance of effector cells capable of recognizing all H-2 antigens, except those coded for by the major histocompatibility loci of the lymphocyte donor. These experiments demonstrate that Con A is capable of activating pre-existing T cells to reveal their genetically determined immunological specificity, and furthermore suggest that there is a deletion of T cell clones with specificity for self. The activated effector cells were characterized as T blasts being relatively insensitive to treatment with anti-O serum plus complement. The precursors of the Con A-activated effector cells were shown to reside primarily in the spleen, to be radio-resistant up to 400 R, and to be short-lived after adult thymectomy. Thus, the population of T cells capable of activation to cytotoxic effector lymphocytes by Con A has similar physical characteristics to the splenic subset(s) of T cells mediating both GVH and cytotoxicity responses upon alloimmunization.

Animals↗

PubMed1976

Human bone marrow lymphocytes. Cytotoxic effector cells in the bone marrow of normal individuals.

This study was undertaken to determine the capability of lymphocytes in the bone marrow of normal individuals to mediate nonspecific killer cell functions in assays of phytohemagglutinin (PHA)-induced cellular cytotoxicity, and antibody-dependent cellular cytotoxicity (ADCC) against 51Cr-labeled chicken erythrocyte target cells. Relatively pure mononuclear cell suspensions were obtained from bone marrow aspirates in 30 normal volunteers by sucrose gradient centrifugations and from the peripheral blood of the same individuals by Hypaque-Ficoll density centrifugations. At an effector: target ratio of 10:1, the PHA-induced cellular cytotoxicity of peripheral blood was 78.8 +/- 1.3%, while that of bone marrow was not significantly less at 66 +/- 9% (P greater than 0.1). At low effector:target ratios, the ADCC of bone marrow was negligible, while at higher effector:target ratios (20:1) bone marrow ADCC was 69 +/- 3.7%, which was comparable to that of peripheral blood. The lymphocytes themselves in the mononuclear cell suspensions of both peripheral blood and bone marrow were capable of cytotoxicity activity since depletion of monocytes from the suspensions by adherence to rayon wool and G-10 Sephadex columns did not remove the cytotoxic activity. Blocking of the Fc receptor on the effector cells by the addition of aggregated gamma globulin to the cultures suppressed the ADCC but not the PHA-induced cellular cytotoxicity of both peripheral blood and bone marrow, indicating that ADCC is dependent on an Fc receptor on the effector cell in both compartments. These studies demonstrate that the bone marrow of normal humans contains populations of lymphoid cells which have highly efficient killer cell capacities. It is uncertain what portion of these cells arise in the bone marrow and what portion enter the bone marrow parenchyma as part of the recirculating lymphocyte pool. These findings have relevance in the clearer understanding of the killer cell potential of grafted human marrow, as well as the bone marrow sequestration of functionally capable lymphocyte subpopulations in disease states and during chemotherapy.

Adult↗

PubMed2025

Diversification, loss, and virulence gains of the major effector AvrStb6 during continental spread of the wheat pathogen Zymoseptoria tritici.

Interactions between plant pathogens and their hosts are highly dynamic and mainly driven by pathogen effectors and plant receptors. Host-pathogen co-evolution can cause rapid diversification or loss of pathogen genes encoding host-exposed proteins. The molecular mechanisms that underpin such sequence dynamics remains poorly investigated at the scale of entire pathogen species. Here, we focus on AvrStb6, a major effector of the global wheat pathogen Zymoseptoria tritici, evolving in response to the cognate receptor Stb6, a resistance widely deployed in wheat. We comprehensively captured effector gene evolution by analyzing a global thousand-genome panel using reference-free sequence analyses. We found that AvrStb6 has diversified into 59 protein isoforms with a strong association to the pathogen spreading to new continents. Across Europe, we found the strongest differentiation of the effector consistent with high rates of Stb6 deployment. The AvrStb6 locus showed also a remarkable diversification in transposable element content with specific expansion patterns across the globe. We detected AvrStb6 gene losses and evidence for transposable element-mediated disruptions. We used virulence datasets of genome-wide association mapping studies to predict virulence changes across the global panel. Genomic predictions suggested marked increases in virulence on Stb6 cultivars concomitant with the spread of the pathogen to Europe and the subsequent spread to further continents. Finally, we genotyped French bread wheat cultivars for Stb6 and monitored resistant cultivar deployment concomitant with AvrStb6 evolution. Taken together, our data provides a comprehensive view of how a rapidly diversifying effector locus can undergo large-scale sequence changes concomitant with gains in virulence on resistant cultivars. The analyses highlight also the need for large-scale pathogen sequencing panels to assess the durability of resistance genes and improve the sustainability of deployment strategies.

Ascomycota↗

PubMed1977

Tumor inhibition by effector cells cultured from progressing sarcomas.

The effect of cytotoxic lymphoid cells emerging in primary cultures of an antigenic sarcoma of strain 13 guinea pigs was investigated on tumor growth in vivo. The growth of lethal tumor inocula was inhibited or the tumor cells were completely rejected in normal syngeneic recipients treated s.c. with low doses (5 X 10(5)) of effector cells which were mixed with the tumor cells. A higher dose (2.5 X 10(6)) of killer cells did not affect significantly tumor growth in normal recipients. Significant tumor inhibition was observed in X-irradiated recipients given high doses (2.2 X 10(6)) of effector cells locally although rejection did not occur with high frequency. Local treatment of X-irradiated recipients with low doses (5 X 10(5)) of effector cells did not influence tumor growth. Systemic treatment of normal or X-irradiated recipients with effector cells had little effect at any dose, although tumor inocula were occasionally rejected. Sonication of the cytotoxic effector cells prior to administration inhibited their tumor suppressing effect. Animals that rejected the first tumor inoculum were immune to a second lethal dose of sarcoma cells. It is indicated by the results that tumor rejection in vivo is not simply a matter of killer-target cell interaction, but rather a complex and poorly understood phenomenon.

Animals↗

PubMed1976

The effector cells in human peripheral blood mediating mitogen-induced cellular cytotoxicity and antibody-dependent cellular cytotoxicity.

The identity of the effector cells in human peripheral blood capable of mediating mitogen-induced cellular cytotoxicity (MICC) and antibody-dependent cellular cytotoxicity (ADCC) was investigated utilizing effector cell populations consisting of purified polymorphonuclear leukocytes, macrophages, lymphocytes, and cell surface immunoglobulin (sIg)-negative and sIg-positive lymphocyte subpopulations obtained by Sephadex anti-Fab immunoabsorbent column fractionation techniques. Chicken erythrocytes (CRBC) and Chang liver cells were used as target cells in both cytotoxicity assays. With CRBC targets MICC was mediated by polymorphonuclear leukocytes, macrophages, sIg-positive lymphocytes (B cells), and sIg-negative lymphocytes. On the contrary, with Chang liver cells as targets, MICC was mediated only by lymphocytes, and effector cells occurred exclusively in sIg-negative lymphocyte subpopulations containing thymus-derived lymphocytes (T cells). Further purification of sIg-negative lymphocyte subpopulations on antigen-antibody coated plastic surfaces yielded a nonadherent T lymphocyte population depleted of Fc receptor-bearing lymphocytes that was capable of mediating MICC against both CRBC and Chang cell targets. With use of CRBC targets, ADCC was mediated by polymorphonuclear leukocytes, macrophages, and sIg-negative lymphocyte subpopulations. However, with Chang cell targets, ADCC was mediated only by lymphocytes, and effector cells were present only in sIg-negative lymphocyte subpopulations. SIg-positive lymphocytes (B cells) and T lymphocytes were not effective in mediating ADCC against either CRBC or Chang cell targets. These studies demonstrate that the nature of the target cell employed in MICC and ADCC reactions is of critical imporatnce in defining the effector cell(s) capable of mediating cytotoxicity.

Animals↗