SEARCH · Search PubMed

Results for “effector”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

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

At least 1,333 records · Page 74Linked to original sources

PubMed1984

[Tumor-specific immunotherapy: active immunotherapy by augmenting the induction of tumor-specific effector T cells through a T-T cell interaction mechanism].

Recent progress in tumor-specific immunotherapy was reviewed. Methods involved include a) utilization of tumor-specific monoclonal antibodies in conjugation with various anti-cancer agents, b) adoptive transfer of anti-tumor effector T cell clones elaborated in vitro in the presence of interleukin-2 and c) active tumor-specific immunotherapy by augmenting the generation of tumor specific effector T cells. This paper focused especially on the amplified induction of tumor-specific immunity by T-T cell interaction between helper T cells and anti-tumor effector T cells. Data were provided indicating successful tumor-specific immunotherapy in autochthonous as well as syngeneic tumor models and such results were discussed in the light of the future clinical application of the tumor-specific active immunotherapy.

Animals↗

PubMed1984

Immunoregulation after thermal injury: sequential appearance of I-J+, Ly-1 T suppressor inducer cells and Ly-2 T suppressor effector cells following thermal trauma in mice.

Immunoregulation as a consequence of thermal injury was investigated by using a murine model involving a 30% surface area full thickness burn. Both allogeneic mixed lymphocyte reaction (MLR) and in vitro anti-SRBC responses were depressed from days 3 to 25 post-burn. Suppressor T cells could be identified in both systems between days 5 and 15. On day 5 post-burn, an Ly-1+,2-, I-J+ T cell is responsible for the majority of the suppression observed. This cell behaves like a T suppressor inducer T cell in that it must interact with an Ly-2+ cyclophosphamide-sensitive cell to manifest suppression. On day 7 post-burn, only Ly-1-,2+ suppressor T cells are found which can directly suppress the activity of Ly-1+,2- helper T cells. Thus, these cells behave as T suppressor effector cells. We suggest that feedback suppression is in operation after thermal injury, with functional suppressor inducer cells appearing on day 5 post-burn, leading to the appearance of T suppressor effector cells by 7 days post-burn. Recovery from post-burn immunosuppression occurs by day 25 post-burn and is associated with the appearance of V. villosa-adherent T cells, whose activity antagonizes that of the day 7 post-burn suppressor effector. These cells may represent contrasuppressor T cells, which could play a role in the restoration of immunocompetence after burn injury.

Animals↗

PubMed1984

Effector mechanisms operative in adoptive therapy of tumor-bearing animals: implications for the use of interleukin-2.

Disseminated tumors growing progressively in syngeneic hosts can be eradicated by combination therapy with cyclophosphamide and adoptive transfer of specifically immune T cells. Interleukin-2 (IL-2), which induces proliferation of T cells specifically activated by antigen, has substantial therapeutic potential as a reagent for increasing the magnitude of tumor-specific T cell responses. The purpose of the present studies was to determine the effector mechanisms operative in tumor-bearing hosts by which subpopulations of immune T cells can mediate tumor eradication, and to determine if the in vivo administration of exogenous IL-2 can augment these T cell effector functions. Disseminated leukemia was eradicated by adoptive therapy with the immune Lyt 1+2- noncytolytic T cell subpopulation, under experimental conditions in which cytolytic T lymphocytes could not participate. The Lyt 1+2- subset contains helper/amplifier cells that produce endogenous IL-2 in response to tumor and effector cells that mediate delayed-type hypersensitivity reactions. The administration of exogenous IL-2 following transfer of immune T cells containing this noncytolytic subset failed to augment their therapeutic activity, implying that the amount of IL-2 being produced endogenously did not limit the antitumor response. Adoptive therapy with purified cytolytic Lyt 1-2+ T cells produced a demonstrable but limited antitumor effect. Since this cytolytic subpopulation lacked helper T cells, the limited activity observed presumably reflected a requirement for an IL-2-producing cell. Administration of exogenous IL-2 following cell transfer satisfied this requirement and markedly augmented the efficacy of adoptive therapy with Lyt 1-2+ T cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1984

Depressed effector activity of OKT4+ and OKT8+ T cell subsets in lectin-dependent cell-mediated cytotoxicity to HEP-2 cells in patients with systemic lupus erythematosus.

The role of OKT4+ and OKT8+ T cell subsets was studied in depressed lectin-dependent cell-mediated cytotoxicity (LDCC) against adherent HEp-2 target cells by peripheral blood mononuclear cells (PBMC) from patients with active systemic lupus erythematosus (SLE). LDCC activity was evaluated by detachment from the monolayer of 3H-TdR-prelabelled HEp-2 cells in a 24 hr assay at 50:1 effector-target cell ratio in the presence of 25 micrograms/ml concanavalin A (Con A). Decreased levels of LDCC were performed by all studied effector cell populations of SLE patients, including both OKT4+ and OKT8+ T cell fractions. LDCC by isolated OKT8+ T cells was superior to that by OKT4+ and unfractionated T lymphocytes from all healthy and SLE subjects. This suggests that the defect of LDCC activity in SLE did not affect the inherently higher LDCC effector activity of OKT8+ to OKT4+ cells. In parallel studies a reduced proliferation of PBMC in response to Con A and failure of OKT8+ T cells to suppress Con A-induced blastogenesis was observed in patients with SLE.

Adult↗

PubMed1983

Purified human monocyte subsets as effector cells in antibody-dependent cellular cytotoxicity (ADCC).

Human peripheral blood monocytes are heterogeneous with respect to their size and function. Two monocyte subsets were isolated by countercurrent centrifugal elutriation and were studied with respect to their ability to effect antibody-dependent cellular cytotoxicity (ADCC) and for the presence of Fc receptors on their surface. Both monocyte subsets display Fc surface receptors and are effectors of ADCC against sensitized human erythrocyte target cells. The demonstration of ADCC by monocyte effectors is dependent on their concentration in the incubation mixture. Dilution of monocytes below 10% by unlabeled and unsensitized erythrocytes or lymphocytes significantly suppresses ADCC, presumably by steric inhibition of effector and target contact.

Antibody-Dependent Cell Cytotoxicity↗

PubMed1983

Defective natural killer activity within human ovarian tumors: low numbers of morphologically defined effectors present in situ.

Tumor-associated lymphocytes (TAL) were isolated from 17 ascites and 7 solid ovarian carcinomas. TAL had defective natural killer (NK) activity against K562. Large granular lymphocytes, the morphologically identified effectors of NK activity, were poorly represented in TAL from ovarian carcinomas as compared to peripheral blood lymphocytes from the same patients or from normal donors. Similar results were obtained when effectors of NK activity were identified with an anti-NK (HNK-1) monoclonal antibody. When four TAL preparations were separated on discontinuous Percoll gradients, they were able to be enriched for NK activity and large granular lymphocyte morphology in the lower density fractions as observed with blood. These observations suggested that a low concentration of the relevant effector cells was the major factor determining the defective NK cytotoxicity of lymphoid cells associated with these human neoplasms.

Antibodies, Monoclonal↗

PubMed1983

Genetically determined resistance to foreign bone marrow transplantation in mice: characterization of the effector cells.

Mice of most strains show a genetically determined ability to reject a variety of foreign marrow grafts even after lethal irradiation. The phenomenon is both host strain and donor marrow graft-dependent. To characterize the effector cell responsible for graft rejection, attempts were made to 1) determine to what morphologic subclass it belongs; 2) determine its life span; and 3) establish whether genetically different host environments influence the functioning of the effector cell. Mice of the 129/J strain (normally nonresistant), C57BL/6 strain (made non-resistant), and the homozygous mutants of C57BL/6, i.e., C57BL/6 (bg/bg), were recipients of C57BL/6 marrow or spleen cells. After lethal irradiation, hosts were given marrow or spleen cells from normal, strongly resistant C57BL/6 donors pretreated with a) 950 R whole body irradiation or b) twice daily injections for 4 days of the cell cycle toxic drug hydroxyurea followed by 950 R. In other cases, hosts were recipients of the lymphoid cell-rich fraction of marrow from irradiated C57BL/6 donors or adherent cells taken from cultures of marrow cells of unirradiated C57BL/6 donors. Three hours after receiving C57BL/6 marrow or spleen cells, irradiated hosts were given allogeneic DBA/2 marrow (always strongly rejected by C57BL/6 mice and always accepted by 129/J strain mice). Seven days later, host spleens were removed and the numbers of microscopic colonies were counted from subserial sections. The results demonstrate that 1) mice either normally or rendered nonresistant to a marrow allograft can be made to develop resistance by the administration of either whole spleen cells or marrow lymphoid cells from lethally irradiated strongly resistant donors; 2) adherent cells from cultures of marrow from strongly resistant mice are ineffective in conferring resistance; 3) the cell effective in conferring resistance has a life span greater than 4 but less than 7 days; and 4) the effector cell can function in genetically different environments of nonresistant strains.

Animals↗

PubMed1981

Expansion of autorecognitive cytotoxic effectors in human cancer by T cell growth factor (Interleukin 2)1.

Conditions for the production of supernates from mitogen stimulated human lymphocytes with the capacity to induce proliferation in long term MLC or PHA stimulated cultures which no longer respond to PHA have been investigated. These supernates can be used to maintain lymphocytes in continuous growth with a doubling time of approximately 48 hours. Cells grown from MLC stimulated cultures show less than 80% SRBC rosetting cells, are Fc-, do not show ADCC activity and induce reduced lysis of K562 compared with freshly isolated effectors. Cultured T cells (CTC) show high lytic activity against the inducing PHA blasts but not autologous or third part targets. Similar experiments have been performed with lymphocytes from the blood, lymph node, spleen and tumour of cancer patients and CTC tested for cytotoxicity against autologous and allogeneic tumour cells and the K562 compared with freshly isolated effectors. Cultured T cells (CTC) show high lytic activity against the inducing PHA blasts but not autologous or third part targets. Similar experiments have been performed with lymphocytes from the blood, lymph node, spleen and tumour of cancer patients and CTC tested for cytotoxicity against autologous and allogeneic tumour cells and the K562 cell line. Cytotoxicity for autologous tumour was found in all samples. This was accompanied by killing of allogeneic cells in most instances but killing of K562 was only rarely demonstrable. These data would be consistent with a polyclonal expansion of cytotoxic effectors in the samples. The finding of autologous reactivity suggests the presence of autorecognitive cytotoxic T cells in cancer patients with specificity for tumour. Cloning experiments are currently in progress to investigate this possibility further.

Cytotoxicity, Immunologic↗

PubMed1982

Communicative interactions between subpopulations of human T lymphocytes required for generation of suppressor effector function in a primary antibody response.

The cellular interactions necessary for generation of human T suppressor effector function were examined in a primary in vitro antigen-specific anti-DNP antibody-forming system. During the induction of the anti-DNP response, it was found that T cells of both T4+ and T8+ subsets were necessary to suppress antibody formation, whereas after activation, only the T8+ subset was required. Thus, a population of T4+ T cells appears to be necessary to activate or induce a subset of T8+ cells to suppress. The T4+ suppressor inducer population, like the resting or activated T8+ suppressor effector subset, was sensitive to low dose irradiation. Moreover, the radiosensitive T4+ subset and the previously defined T4+JRA+ subset were shown to be functionally similar or complementary in that both were required for generation of suppressor effector function. These findings suggest that T-T interactions between radiosensitive T4+JRA+ T cells and radiosensitive T8+ T cells are necessary for suppression of primary antigen-specific antibody production in man.

Antibody Formation↗

PubMed1983

Heterogeneity of human NK cells: comparison of effectors that lyse HSV-1-infected fibroblasts and K562 erythroleukemia targets.

In this study, we compared the natural killer (NK) cells that lyse HSV-1-infected NK(HSV-1) or uninfected [NK-(FS)] fibroblasts to those that lyse K562 erythroleukemia cells [NK(K562)]. Activity against all three targets was found in Percoll gradient fractions enriched for large granular lymphocytes, which suggests that these effector cells have a common morphology. In competition studies between 51Cr-labeled targets and unlabeled targets, both the infected and the uninfected fibroblasts competed for lysis of NK(HSV-1) and NK(FS) activity, whereas K562 cells competed poorly. In contrast, when 51Cr-labeled K562 cells were used, the unlabeled K562 cells competed well, but HSV-1-infected and uninfected fibroblasts competed poorly. Panning studies and complement elimination experiments using monoclonal antibodies were performed to describe cell surface markers on the NK cell populations. Treatment with an antibody to an la framework antigen reduced NK(HSV-1) but not NK(K562) activity. In contrast, the majority of NK(K562) effectors were recognized by antibodies to the E-rosette receptor (Lyt-3 and OKT11A), whereas NK(HSV-1) activity was much less sensitive to this antibody. OKM1, OKT10, and Leu-7 (HNK-1) markers were found on a portion, but not all, of the cells that lysed both the HSV-FS and K562 targets, while treatment with HLA plus complement totally abrogated both NK activities. Taken together, these data are consistent with the concept that human NK cells are heterogeneous and that we are dealing with at least three subpopulations of effector cells--one that kills the infected or uninfected fibroblasts; one that kills K562 cells; and a third population that may be able to kill all three targets. Patient studies provide additional evidence for heterogeneity within the NK cells that lyse the fibroblasts and K562 cells. We have studied a number of individuals who have normal NK activity with one target (HSV-FS or K562) but have low or no activity against the other. These patients provide strong evidence not only that NK cells are heterogeneous but also that these NK subpopulations can be regulated independently of each other in vivo.

Adult↗

PubMed1980

Analysis of cytotoxic effector cell function in patients with leukemia or aplastic anemia before and after marrow transplantation.

Cytotoxic effector cells mediating natural killing (NK), antibody-dependent cellular cytotoxicity (ADCC), and lectin-dependent cellular cytotoxicity (LDCC) were studied in patients with leukemia or aplastic anemia before and/or after marrow transplantation. Before transplantation, about one-third to one-half of the patients were deficient in cytotoxic activity. In patients with leukemia, this was most likely due to large numbers of circulating blast cells diluting or replacing the effector cells. In patients with aplastic anemia there was an apparent absence of the effector cells in a proportion of the patients. After marrow transplantation, cytotoxic activity in all three systems returned to normal rapidly, by 30 days, and remained so through 100 days. However, about 20% of patients studied beyond 1 year were deficient in these functions. There were no significant associations between cytotoxic activity and important clinical parameters including infections, graft-vs-host disease, and recurrence of leukemia. Our findings do not support an immunosurveillance role for NK against leukemia after marrow transplantation. Furthermore, they point out the need for new in vitro approaches for meaningful monitoring of marrow transplant patients. Finally, our results showed a significant discordance between NK, ADCC, and LDCC activities in these immunologically perturbed individuals, indicating that either different cell populations or different cellular mechanisms are involved in these cytotoxic functions.

Anemia, Aplastic↗

PubMed1981

Lymphocyte-mediated cytotoxicity against allogeneic tumour cells. IV. Fine specificity mapping and characterization of concanavalin A-activated cytotoxic effector lymphocytes.

Concanavalin A (Con A)-activated cytotoxic lymphocytes have been investigated, mapping the genetic differences between the P815 target and the effector cells required for cell-mediated lympholysis to occur. The target antigens recognized during the effector phase and the phenotype of the killer cell population(s) were also determined. It was found that Con A could activate a population of primed cytotoxic lymphocytes capable of killing target cells that were identical at the major histocompatibility complex (MHC) but differed at other background genes. Thus, after in vivo priming with DBA/2, B10.D2 lymphocytes cultured with Con A were capable of killing the P815 target. Unprimed B10.D2 cells, however, would not. Studies on the involvement of the MHC indicated that differences in the H-2K through H-2S, as well as differences in H-2D and H-2L alone could cause lysis. This killing could not be accounted for by additional differences at Qa-2, a MHC-linked locus. However, the contribution of other similar non-MHC linked loci could not be excluded. Cold target competition experiments indicated that MHC encoded alloantigens were involved as recognition structures on the target cell surface. Antisera plus complement depletion of cytotoxic effector function demonstrated that the cytotoxic cells had the cell surface phenotypes Thy 1.2+, Lyt 2.2+ and natural killer (NK) 1.1-. We conclude that Con A polyclonally activates population(s) of T cells that express antigen-specific cytotoxicity through clonally distributed recognition receptors intrinsic to their membranes when lectin is omitted from the cytotoxic assay.

Animals↗

PubMed1980

Surface markers on the T cells that regulate cytotoxic T cell responses. II. Distribution of Ly 6.1 and Ly 7.2: selective expression of Ly 7.2 on helper T cell effectors.

Helper T cells and suppressor T cells can be generated in vitro, yielding effector cells with radioresistant function that regulate a cytotoxic T cell response to alloantigen. The Ly 6.1 and Ly 7.2 antigen phenotype of these regulatory effector cells has been determined. Ly 7.2 was found to be selectively expressed on helper T cells; neither the suppressor cells nor the cytotoxic cells analyzed here were found to bear Ly 7.2 antigens. Mixing experiments demonstrated that the helper cell bears both Ly 1.1 and Ly 7.2. Removal of help by anti-Ly 7.2 treatment frequently enhanced suppressor activity. Suppressive activity was partially depleted by treatment with anti-Ly 6.1; helper cell activity was unaffected by such treatment. Cytotoxic T cell precursors bear neither Ly 6.1 nor Ly 7.2, but approximately half of the cytotoxic T cell effectors did bear Ly 6.1; none bore Ly 7.2. Analysis of populations depleted of 7.2-bearing cells should therefore allow the design of experiments that will increase our understanding of the interactions of various regulatory cell populations in the control of a cytotoxic T-cell response.

Animals↗

PubMed1978

Human lymphoblastoid cell lines as effector cells in mitogen-dependent and antibody-dependent cell-mediated lysis.

Based on reports that both human and murine lymphoblastoid cell lines can effect lysis in antibody-dependent (ADCC) and mitogen-induced (MICC) cell-mediated cytotoxicity, 10 human lymphoblastoid cell lines were investigated for their ability to act as effector cells in these lytic reactions. Four cell lines promoted MICC and ADCC of chicken erythrocytes. MICC was inhibited by subjecting the effector cells to gamma-irradiation, and ADCC was partially inhibited by treating antibody-coated target cells with Protein A from Staphylococcus aureus. The latter finding suggests that antibody plays a role in the cytotoxic reaction. The lytic activity of cultured human lymphoid cells in both MICC and ADCC reactions was, however, quite variable for unknown reasons. Because of this instability human lymphoblastoid cell lines are not a suitable source of effector cells for studying the biological and molecular properties of structures responsible for the lytic reaction.

Animals↗

PubMed1981

The mechanism of specific suppression in effector T cell clones against tumor-associated transplantation antigens.

The present study investigates the fate of effector T cell population against tumor-associated transplantation antigens (TATA) of X5563 plasmacytoma in syngeneic mice rendered specifically unresponsive to the TATA. In this tumor system T cell-mediated tumor-specific immunity was induced by intradermal inoculation of viable tumor cells followed by the surgical resection of the tumor (immunization procedure). The intravenous (iv) presensitization of syngeneic hosts with X-irradiated tumor cells abolished the capability of those hosts to develop the tumor-specific immunity after the above appropriate immunization procedure. Spleen cells from the pretreated mice which subsequently received the immunization procedure could not regain the tumor-neutralizing activity after enzymatic treatment with papain. Moreover, lymphoid cells from the pretreated mice could not be stimulated by the immunization procedure even after proteolytic treatment with papain or trypsin, followed by transfer into other recipient mice free of the serum suppressive factor(s). On the other hand, such enzyme treatment was capable of preventing the tolerance induction of dinitrophenyl (DNP)-primed B cells after in vitro pulsing with DNP-D-GL (copolymer of D-glutamic acid and D-lysine) for 2 hr, suggesting that the enzymatic treatment used here was adequate to remove the blocked receptor and any tolerogen. These results suggest that in X5563 plasmacytoma system, the above specific unresponsiveness induced by the iv presensitization with TATA is due to the irreversible inhibition or deletion of effector T cell clones rather than mere effector cell blockade.

Animals↗

PubMed1982

Macrophages as effector cells of protective immunity in murine schistosomiasis. III. Loss of susceptibility to macrophage-mediated killing during maturation of S. mansoni schistosomula from the skin to the lung stage.

Newly transformed skin-stage and lung-stage schistosomula were compared in terms of their susceptibility to killing mediated by activated mouse macrophages in vitro. Although skin-stage schistosomula were readily killed by macrophages activated as a consequence of either BCG or Schistosoma mansoni infection and used either as cell monolayers or in suspension, lung-stage larvae appeared to be totally resistant to this effector mechanism and survived normally when reinjected into mice. Resistance of schistosomula to in vitro damage by macrophages was evident as early as 18 hr after host infection and was complete in worms recovered at 42 hr. The insusceptibility of lung-stage larvae is apparently not due to a defect in effector cell-target contact, because the induction of extensive macrophage adherence to the worms by the addition of anti-mouse red blood cell antisera to the cultures had no effect on parasite viability. These findings provide additional support for the concept that schistosomula during their development to the lung stage undergo a generalized change affecting their susceptibility to a variety of different immunologic effector mechanisms.

Aging↗

PubMed1978

[Analysis of the regulatory influence of effector cells on 3H-catecholamine synthesis in an adrenergic neuron].

In isolated organs of the white rats activation of noradrenaline-H3 and dophamine-H3 synthesis during action of the alpha-adrenoblocking agent phentolamine (1.10(-6) M) and inhibition of the amines synthesis under influence of the alpha-adrenoreceptor activator mezaton (1.10(-5) M) were due to a release from cells-effectors of respective humoral factors and to the latters' effect upon the processes of amine formation in the adrenergic neuron. Formation of the humoral factors altering the rate of catecholamines-H3 synthesis is associated with activation of the protein synthesis in cells-effectors and occurs during change of the functional state (excitation or blockade) of the post-synaptic adrenoreceptors. The processes occurring at the time in the adrenergic neuron, are not correlated with protein formation. The possibility of existence of a common mechanism for feed-back transsynaptic regulation of synthesis and neuronal uptake of noradrenaline via adrenoreceptors of cells-effectors by means of changing the intensity of thyrosin and noradrenaline transport into the neuron is discussed.

Adrenergic Fibers↗

PubMed1980

Antibody-dependent cell-mediated cytolysis (ADCC) with antibody-coated effectors: new methods for enhancing antibody binding and cytolysis.

When P388D1 cells are incubated with anti-TNP IgG antibody and centrifuged through a mixture of dibutylphthalate and bis-(2-ethylhexyl)phthalate (1.5:1), large amounts of antibody remain cell bound for at least 20 hr after washing. Incubating cells with antibody in various concentrations of polyethylene glycol also enhances antibody binding compared with control cells incubated with antibody alone. P388D1 cells coated with anti-TNP antibody are potent killers of TNP-conjugated chicken erythrocytes (not coated with antibody). The cytolytic activity increases in proportion to the amount of antibody bound by the effector cells. Lysis is antibody dependent and hapten inhibitable. When mediated by antibody-coated effectors, lysis is less suceptible to inhibition by aggregated IgG than lysis of antibody-coated cells mediated by untreated effector cells.

Animals↗