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[Examination of the action of effectors after storing glutamine synthetase from the fodder yeast Candida tropicalis at room temperature].

The pattern of action of effectors (AMP, IMP, CMP, anthranilic acid, tryptophane, alanine, glutamine, glycine, histidine) and glutamine synthetase (GS) extracted from the fodder yeast Candida tropicalis and stored at room temperature for 1.5-2 hrs was examined. As regards the action of effectors on GS after its exposure at room temperature, they can be subdivided into four groups: 1) the effector loses completely its inhibitory effect (glutamine, CMP, anthranilic acid in the synthetase reaction); 2) the inhibitory effect on the enzyme increases (AMP, IMP, anthranilic acid in the transferase reaction); 3) at low concentrations of the effector the peak of activation appears (tryptophane, GMP, alanine, glycine); 4) at low concentrations of the enzyme two peaks of activation appear (histidine). Similar results were obtained with the purified preparation of GS.

Amino Acids↗
PubMed1985

Immunological cellular regulator and effector mechanisms in myocarditis.

The diagnosis, pathogenesis and etiology of myocarditis are often difficult to establish with certainty. Consequently, we investigated cellular regulator and effector mechanisms in patients with viral heart disease (Coxsackie B3, influenza, EBV, mumps) as well as other inflammatory heart diseases which could not be classified etiologically. In acute myocarditis there was an elevation of B- and activated T-lymphocytes (OKIa 1-positive) but, in contrast, no significant changes in the activity of peripheral suppressor T-cells (OKT 8-positive). The activity of cell-specific lymphocytic effector mechanisms against vital cardiocytes was unchanged or slightly elevated in myocarditis, while the activity of the less target cell specific natural killer cells, which were measured in vitro against K562 tumor cells, was diminished. These findings are indicative of increased activity of target specific cytotoxic effector mechanisms and a reduction in the activity of nonspecific cellular effector mechanisms in peripheral blood.

Animals↗
PubMed1986

Characterization of human cytotoxic lymphocytes directed against cells infected with typhus group rickettsiae: evidence for lymphokine activation of effectors.

An in vitro culture and assay system was used to determine whether cytotoxic lymphocytes are generated in humans after rickettsial infection. Peripheral blood mononuclear cells (PBMC) were obtained from six individuals with serologic evidence of prior infection with typhus group rickettsiae and from six nonimmune individuals. After PBMC from immune individuals were stimulated in vitro for 7 days with rickettsial antigen, they were capable of lysing typhus group rickettsia-infected, autologous phytohemagglutinin (PHA)-induced blasts, but not uninfected PHA-blasts. No cytotoxic effector cells were generated when either PBMC from immune individuals were placed in culture for 7 days without antigenic stimulation, or when PBMC from nonimmune individuals were stimulated in vitro with antigen for 7 days. Freshly isolated PBMC from immune donors were also unable to lyse typhus group rickettsia-infected autologous PHA-blasts or an autologous rickettsia-infected lymphoblastoid cell line (LCL). Neither supernatants from antigen-stimulated cultures of PBMC from immune donors nor recombinant human interferon-gamma were capable of significantly lysing typhus group rickettsia-infected PHA blasts by this assay. Populations of cytotoxic effector cells depleted of OKT3, OKT4, or OKT8-positive cells by treatment with the respective monoclonal antibodies and complement were assayed for their cytotoxic capacity. The results suggest that the cytotoxic effector cell population is predominantly OKT3 and OKT8-positive, but OKT4-negative. Positive selection with the use of a fluorescence-activated cell sorter also suggested that most of the cytotoxic effector cells are OKT8-positive. PBMC from immune donors after in vitro stimulation with rickettsial antigen were capable of significantly lysing infected autologous LCL or infected HLA-mismatched LCL as compared with the respective uninfected controls. In addition, PBMC from either immune donors or nonimmune donors after stimulation in vitro for 7 days with media containing purified lymphokines were capable of significantly lysing autologous infected LCL as compared with the uninfected autologous control. We conclude that lysis of cells infected with typhus group rickettsiae is mediated by a lymphokine-activated killer.

Antigens, Bacterial↗
PubMed1986

Interferon and butyrate treatment leads to a decreased sensitivity of NK target cells to lysis by homologous but not by heterologous effector cells.

Human K-562 and HHMS cells were pretreated with human recombinant interferon (IFN)-gamma and used as targets in NK assays against human and murine effector cells. A protective effect against NK lysis was observed only in the homologous assay, whereas no change or even a slight increase in NK sensitivity against heterologous effector cells was found. In cold target inhibition experiments IFN-treatment of K-562 cells led to a decrease in their capacity to act as competitors in the homologous NK assay, leaving their inhibitory capacity unaltered in the heterologous assay. In accordance with results observed using human NK targets, murine YAC-1 cells treated with mouse recombinant IFN-gamma did not lose their susceptibility to human NK cells. However, they were markedly less susceptible to lysis mediated by murine effectors. Butyrate, another compound causing decreased sensitivity of K-562 cells for human natural killing, also failed to reduce the susceptibility against murine NK cells. The results indicate that the NK-resistant tumor target phenotype caused by IFN or differentiation-inducing agents can only be detected by homologous but not by heterologous effector cells. This suggests that major differences exist between the inter- and intraspecies NK killing mechanisms.

Animals↗
PubMed1987

Autoimmune effector cells. IX. Inhibition of adoptive transfer of autoimmune encephalomyelitis with a monoclonal antibody specific for interleukin 2 receptors.

This study was conducted to determine whether a monoclonal antibody (MAb) specific for rat interleukin 2 receptors (IL 2R) inhibits the activation of effector T cells that adoptively transfer experimental allergic encephalomyelitis (EAE). MAb OX 39 appears to be specific for IL 2R because it binds to concanavalin A-activated, but not resting, rat lymphocytes and inhibits mitogen- and IL 2-induced proliferation of rat spleen cells. Moreover, this MAb inhibits the in vitro activation of effector cells of EAE by myelin basic protein when added to immune donor spleen cell at the start of 72-hr culture or after 24 hr, but not when added after 48 hr of culture. Other studies employed MAb W3/25, which reacts with the rat helper T cell subset and appears to define the rat homolog of the human CD4 marker present on T4-positive cells. MAb W3/25 also blocks in vitro activation of EAE effector cells, and this blocking effect can be abrogated by adding rat T cell growth factor or partially purified IL 2 to the donor spleen cell cultures. T cell growth factor alone is incapable of activating EAE effector cells. These findings are discussed with respect to the role of lymphokines in the generation of autoreactive T cells.

Animals↗
PubMed1988

Transmembrane chloride flux is required for target cell lysis but not for Golgi reorientation in cloned cytolytic effector cells. Golgi reorientation, N alpha-benzyloxycarbonyl-L-lysine thiobenzyl ester serine esterase release, and delivery of the lethal hit are separable events in target cell lysis.

Cell-mediated cytotoxicity can be inhibited by the replacement of chloride with ions that are incapable of passing through chloride channels or by the presence of stilbene disulfonate derivatives known to interfere with chloride flux. We show that the stilbene disulfonate (4,4-diisothiocyano-2,2'-disulfonic acid stilbene (DIDS) inhibits lysis of YAC-1 targets by the cloned cell line NKB61A2. Inhibition of lysis occurs on the level of the effector cell inasmuch as preincubation of effectors but not of targets interferes with subsequent lysis. Moreover, inhibition of chloride flux in the target does not interfere with target cell lysis by cytotoxic granules isolated from killer cells. Target cell binding takes place in the presence of DIDS or absence of external chloride, suggesting that events that follow target cell binding require chloride flux. We show that reorientation of the Golgi apparatus, which occurs subsequent to target cell binding in the effector cell, occurs under conditions that interfere with chloride flux. It is therefore suggested that events in the effector cell taking place subsequent to the Golgi apparatus reorientation reaction are inhibited and that delivery of the lethal hit is a stimulus-induced secretory event that requires transmembrane chloride flux. Delivery of the lethal hit is shown to be independent of the release of N alpha-benzyloxycarbonyl-L-lysine thiobenzyl ester (BLT) serine esterase, suggesting that cytolytic components and BLT serine esterase are likely packaged in different vesicles.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1988

Effector mechanism of tumor immunity in murine plasmacytoma.

The development of concomitant tumor immunity to plasmacytoma (PC) was previously demonstrated by the detection of splenic immune T-lymphocytes that inhibited the growth of PC in local adoptive transfer (Winn) assay. This immunity was down-regulated by cyclophosphamide-sensitive suppressor T-cells. The effector mechanism was further studied. It was found that immune spleen cells contained no cytotoxic T-lymphocytes as determined by 51Cr release assay. Immune spleen cells, however, exerted a cytostatic effect on PC cells in vitro; coculture of immune spleen cells with PC cells inhibited the [3H]thymidine uptake by tumor cells. No in vitro generation of cytolytic activity was observed. The cytostatic effector cells were found to be radiosensitive, nonadherent, Thy-1+, Lyt-1-2+ lymphocytes that required direct cell-cell contact for cytostasis. Plasmacytoma arising from transplants of mixtures of PC cells and immune spleen cells had a slower growth rate in vivo and incorporated less [3H]thymidine in vitro, findings consistent with the cytostatic effect of immune spleen cells. Studies comparing cytostatic cells assayed in vitro and immune splenic effector cells assayed in vivo (Winn assay) revealed that the former were short-lived (less than 26 days), high dose cyclophosphamide (200 mg/kg) resistant, and cross-reacting to other PC, whereas the latter were long-lived (greater than or equal to 102 days), high dose cyclophosphamide sensitive, and individual tumor specific. Immune spleen cells, however, could inhibit heterologous PC growth in vivo, if the homologous PC were also present. These findings are consistent with the hypothesis that the concomitant tumor immunity in PC involves terminal cytostatic effector T-cells with a broader target spectrum and tumor-specific helper T-cells that are required for clonal expansion and maturation of cytostatic cells in vivo.

Animals↗
PubMed1988

Identification and selection of human lymphokine activated killer cell effectors and novel recycling intermediates by unique light-scattering properties.

When peripheral blood lymphocytes (PBL) are incubated with interleukin 2 (IL 2), a novel cytotoxic lymphocyte subpopulation, termed lymphokine activated killers (LAK), arises. LAK are functionally defined as IL 2 responsive cells demonstrating major histocompatibility antigen-unrestricted cell-mediated cytotoxicity against fresh solid tumors and other natural killer cell-resistant and -sensitive tumor targets in the absence of prior antigen priming. Flow cytometric analysis of IL 2 activated PBL using forward and right angle light scatter and fluorescence intensity identified the emergence of a large, optically dense, autofluorescent cell population which paralleled the generation of LAK activity. These unique IL 2 induced lymphocytes have been named giant autofluorescent lymphocytes (GAL). These cells are readily distinguished from the small nonfluorescent lymphocytes (SNL) observed in fresh PBL, unstimulated cultured PBL, and those cells remaining after incubation with IL 2 which have not acquired GAL characteristics. In this investigation, LAK cultures were sorted on days 4, 5, and 6 into GAL and SNL populations and were tested for oncolytic activity against the natural killer-resistant Daudi and RC-1 tumor targets. Against these targets, lymphocytes from non-IL 2 activated PBL or the sorted SNL population expressed less than 2% of the oncolytic activity (measured in lytic units) exhibited by GAL effectors. The SNL and GAL populations were cultured in IL 2 for up to 48 h following the sorting procedure and then reassayed for tumor cytolytic activity. During this culture period, GAL but not SNL continued to express LAK killing against natural killer-resistant tumor targets. Using gamma-irradiation to prevent further cell cycling, it was shown that the functional half-life of the LAK effector was approximately 8.5 h. Therefore, the cytotoxicity expressed by the sorted GAL population after 48 h in culture (equivalent to five functional half-lives) must be expressed by progeny of the originally plated lymphocytes. These results indicate that in addition to the LAK effector, the GAL population contains a self-sustaining, recycling intermediate responsible for generating new LAK. Our data indicate that analysis of IL 2 activated PBL using GAL light-scattering properties has application in phenotyping LAK, monitoring of cellular kinetics, cell sorting, and enrichment of the LAK effector population, and in the clinical monitoring of IL 2 therapy.

Cell Cycle↗
PubMed1987

Antitumor activity of a Streptococcus pyogenes preparation (OK-432). I. Sequential effector mechanisms following a single OK-432 injection in F344 rats leading to the rejection of syngeneic MADB106 tumor cells.

The effector mechanisms evoked in tumor-bearing rats following a single injection of the avirulent Su strain of type 3, group A Streptococcus pyogenes (OK-432) were sequentially examined. F344 rats challenged ip with a lethal dose of the syngeneic MADB106 mammary carcinoma could survive more than 100 days when given 50 mg OK-432/kg ip 1 day after tumor challenge. When the responsible effector mechanisms were examined in this therapeutic model, two distinct effector phases distinguished by the number of tumor cells were evident. Phase I, 1-6 days following OK-432 injection, resulted in a sharp decrease in tumor cell numbers and was related to the direct antitumor cytotoxicity of OK-432 and was coincident with an increase in the number of polymorphonuclear neutrophils. However, by day 6 a sharp increase in tumor cell numbers was again observed. Subsequently, a second phase of tumor cell destruction was observed 7-20 days following OK-432 injection and was reflected in a strong lymphocyte-mediated cytotoxicity response as well as the production of complement-dependent cytotoxic antibody against the MADB106 tumor cells. Further, the adoptive transfer of either peritoneal exudate cells or sera from the phase II animals revealed that both factors may be responsible for the antitumor activity observed in this therapeutic model. In conclusion, this study has demonstrated that the antitumor effects seen with OK-432 are due to a combination of sequential effector mechanisms leading to the eventual rejection of established tumor.

Animals↗
PubMed1986

In vitro sensitization and expansion with viable tumor cells and interleukin 2 in the generation of specific therapeutic effector cells.

We have investigated the efficacy and immunologic characteristics of immune effector cells generated from cultures containing large numbers of viable tumor cells and interleukin 2 (IL 2) in the adoptive immunotherapy of experimentally induced pulmonary metastases from the newly developed, weakly immunogenic MCA 105 sarcoma in mice. The current culture conditions allowed increases of either normal or MCA 105 immune spleen cells up to 94-fold in 15 days. The in vitro expanded normal and MCA 105 immune cells displayed nonspecific in vitro cytotoxicity against several syngeneic tumor targets. However, therapeutically effective cells could only be obtained from cultures initiated with MCA 105 immune spleen cells. Immunotherapy with expanded immune effector cells could lead to the reduction of established 3 day pulmonary metastases, prolongation of survival, and cure of tumor in the majority of animals. The generation and proliferation of therapeutic effector cells in vitro depended on the presence in cultures of specific tumor stimulator cells as well as the presence of IL 2. Although immunotherapy with either fresh noncultured or secondarily in vitro-sensitized (IVS) MCA 105 immune spleen cells was immunologically specific, the efficacy of the adoptive cellular therapy with cultured but not fresh immune cells could be improved by the administration to tumor-bearing hosts of exogenous IL 2. In addition to numerical expansion, the IVS immune cells, on a per cell basis, afforded an eightfold to 10-fold increase in therapeutic efficacy when compared with fresh noncultured MCA 105 immune cells. Our results indicate that the current culture procedure induced in vitro antigenic stimulation and expansion of tumor-specific immune effector cells that was otherwise not possible by conventional mixed lymphocyte-tumor cultures.

Animals↗
PubMed1987

Analysis of the murine lymphokine-activated killer (LAK) cell phenomenon: dissection of effectors and progenitors into NK- and T-like cells.

Murine as well as human lymphokine-activated killer (LAK) cells have been reported to have several characteristics of T lymphocytes and to be clearly distinct from natural killer (NK) cells. The present study of murine LAK cells showed that cytotoxic cells generated in the presence of interleukin 2 IL 2 were heterogeneous with respect to cell surface markers of progenitor as well as effector cells. Negative selection of cells with antibodies and complement or positive selection by fluorescence-activated cell sorting unequivocally showed that LAK effector cells consisted of at least two clearly distinct populations, the relative contribution of which was dependent on donor organ and target cells studied. Approximately 40% of the cytotoxic activity of spleen-derived effector cells active against the NK-resistant targets EL-4 or MCA-5 was eliminated by treatment with antibodies to the NK-markers asialo-GM1 and NK 1 (NK-LAK). Approximately 60% of cytotoxic activity was associated with cells expressing the T cell marker Lyt-2, lacked NK 1, and was lacking or expressed only small amounts asialo-GM1 (T-LAK). The NK-LAK cells were of greater importance for the cytotoxic activity against the standard NK target YAC-1, although T-LAK cells also excerted significant cytotoxicity against this cell line. Limiting dilution analysis estimated that the minimal frequency of precursors developing into cells with cytotoxic activity against EL-4 was 1/6700 in spleen and 1/4200 in peripheral blood. The frequency of cells developing into cytotoxic effectors against YAC-1 cells was 1/3700 and 1/1450 in spleen and peripheral blood, respectively. Depletion of progenitor cells from spleen or peripheral blood expressing NK 1 or Lyt-2 by treating the cells with antibodies to these structures and complement indicated that NK-1-expressing cells were the dominating progenitor of the LAK cells irrespective of target cells used. Culture of murine lymphoid cells from spleen or peripheral blood with high concentrations of IL 2 results in the emergence of two different killer cell populations with phenotypic similarities to NK and T cells, respectively, both being able to kill targets resistant to resting NK cells. In contrast to numerous earlier reports, we concluded that LAK cells are heterogeneous with respect to surface markers, with a major population of LAK cells apparently representing IL 2-activated cells expressing cell surface markers associated with NK cells.

Animals↗
PubMed1987

Cytolytic activity of human peripheral blood leukocytes against Legionella pneumophila-infected monocytes: characterization of the effector cell and augmentation by interleukin 2.

The present study was an in vitro attempt to define the effector mechanisms against the intracellular bacterium Legionella pneumophila. Monocytes from human peripheral blood leukocytes (PBL) were infected in vitro with L. pneumophila and cultured for 2 days to allow intracellular replication of the bacterium. Cells were then labeled with 51Cr and used as targets in a 4-h 51Cr-release assay. We report here that autologous nonadherent PBL effectively lysed infected monocytes, and this activity was enhanced when the effector cells were precultured with IL 2 for 2 days. The IL 2-activated killer cells were also cytolytic against uninfected cultured monocytes, but cytotoxicity was higher against Legionella-infected target cells in a dose-dependent manner. The effector cells were located in Percoll density fractions that were enriched for large granular lymphocytes. The phenotype of the effector cell activated by IL 2 was determined to be OKM1+, OKT11+, partially Leu-11+, and negative for Leu-M1, OKT4, OKT8, and Leu-7, indicating that it is neither a T cell nor a monocyte, and is possibly and NK subset that is Leu-11+ and Leu-7-. Cold target inhibition studies indicated that a similar recognition structure is shared by both infected and uninfected monocytes, but differs from that on K562 tumor target cells. Thus, in addition to tumor surveillance and controlling viral infections, killer cells can be activated to provide protection against intracellular bacterial infections.

Antibodies, Monoclonal↗
PubMed1979

Evidence that natural cytotoxicity and antibody-dependent cellular cytotoxicity are mediated in humans by the same effector cell populations.

The present study strongly suggests that, in humans, natural killer (NK) activity and antibody-dependent cell-mediated cytotoxicity (ADCC) are mediated by the same effector cell population. This is supported by two different experimental approaches. First, competition for NK effector cells was accompanied by simultaneous inhibition of ADCC activity. Target cells sensitive to NK activity were capable of inhibiting specifically an ADCC assay in cold target competition experiments. Second, specific removal of NK cells on monolayers formed by target cells sensitive to NK activity caused simultaneous depletion of ADCC effector cells. In association with the removal on the monolayers of effector cells for ADCC as well as NK activity, we also found a significant depletion of cells bearing Fc gamma receptors.

Antibody Specificity↗
PubMed1985

[Comparative analysis of the action of thymic and cerebral GD3 gangliosides on the sensitivity of tumor cells to natural splenic effectors].

Thymic gangliosides GM3 and GD3 and LacCer incorporated into the membrane of the tumor target cell leukemia (YAC) increase its sensitivity to the membrane toxic action of spleen effectors. Unlike thymic gangliosides GD3, ganglioside GD3 of the brain origin substantially reduces tumor cell sensitivity to spleen effectors. Some other brain glycosphingolipids differing essentially in the structure of the carbohydrate part of the molecule exert the same action. It has been shown in model experiments with incorporation into the tumor cell membrane of brain ganglioside GD3 combined with thymic LacCer or with egg phosphatidylcholine that the increase in the sensitivity of the tumor cell membrane to spleen effectors is linked with a change in the properties of the lipid membrane matrix under the effect of unsaturated fatty acids (e.g. in experiments with phosphatidylcholine). It follows from the data presented that the capability of influencing the sensitivity of tumor cells to natural spleen effectors largely depends on the differences in the structure of the cearamide part of brain and thymic GD3.

Animals↗
PubMed1983

Characterization of human effector and suppressor T cells by their activity in mixed lymphocyte reaction and by monoclonal antibody phenotyping.

Human T effector and T suppressor cell subpopulations which are functionally operative in the local graft-versus-host reaction were enriched and separated on the basis of their respective ability to form (or not to form) rosettes with sheep red blood cells in the presence of theophylline. These subpopulations were then tested as stimulators and as responders in the allogeneic mixed lymphocyte reaction assay against the same mononuclear cells. Among 18 normal donors, theophylline resistant cells responded more vigorously to mononuclear cells (SI, 9.9 +/- 9.8) than theophylline-sensitive cells (6.7 +/- 5.7, p less than 0.08). In contrast, T-effector cells were poorer stimulators of the same MNC (SI, 4.0 +/- 5.6) when compared to the stimulatory capacity of T suppressor cells (SI, 7.1 +/- 9.8, p less than 0.05). Similar studies among 14 patients with disseminated cancer showed the same, but more pronounced differences. Thus, the theophylline-resistant T effector cells were vigorous responders (SI, 14.7 +/- 10.0) compared to the weak response of the theophylline-sensitive T suppressor cells to the same mononuclear cells (SI, 3.4 +/- 1.8, p less than 0.01). Again, in contrast, T effector cells stimulated mononuclear cells poorly (SI, 1.0 +/- 0.5) while T suppressor cells induced a weak but significant stimulation (SI, 3.2 +/- 2.1, p less than 0.05). Phenotyping of these two functionally distinct subpopulations with monoclonal antibodies to subsets of T cells (Leu I, II, III) and for the HLA-DR antigen (OKIal) showed no enrichment for any of the phenotypes as defined by these antibodies.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗
PubMed1982

Maximal limits of the Escherichia coli replication factor Y effector site sequences in pBR322 DNA.

pBR322 DNA contains two separate regions on opposite strands and close to the origin of replication which, when in single-stranded form, can act as effectors for the ATPase activity of Escherichia coli replication factor Y. Small fragments of DNA containing these sites when cloned into an fl phage vector act as origins of DNA replication allowing the formation of complementary double-stranded DNA in a rifampicin-resistant, dnaB-, dnaG-, and dnaC-dependent fashion in vitro. We report here the maximal limits of the E. coli replication factor Y effector sites of pBR322 DNA. The site on the H strand of pBR322 DNA can form a structure resistant to digestion by E. coli exonuclease VII, the site on the L strand cannot. The H and L strand sites lie within nucleotides 2144-2185 and 2353-2416, respectively, of pBR322 DNA. A deletion of 34 nucleotides (nucleotides 2121-2154) within the H strand site renders it totally inactive as an effector for factor Y ATPase activity. No extensive homology could be detected between the three known factor Y effector sites, the two reported here and the one previously identified on the phi X174 viral DNA strand (Shlomai, J., and Kornberg, A. (1980) Proc. Natl. Acad. Sci. U. S. A. 77, 799-803).

Adenosine Triphosphatases↗
PubMed1984

Cell contact-mediated macrophage activation for antileishmanial defense. II. Identification of effector cell phenotype and genetic restriction.

Host defense in cutaneous leishmaniasis, due to Leishmania tropica, is largely--if not exclusively--cell mediated. We observed in vitro that draining lymph node lymphocytes from L. tropica-infected C57BL/6 mice activate L. tropica-infected macrophages to kill the intracellular parasites (leishmanicidal effect). Because direct cell contact between lymphocytes and infected macrophages is required to achieve a maximum leishmanicidal effect, this effect cannot be attributed solely to lymphokines. Furthermore, because effector lymphocytes induced no detectable damage to infected macrophages, the effect also differs from conventional lymphocyte-mediated cytotoxicity. The present study identifies the phenotype of the effector lymphocyte and assesses the genetic restriction of the lymphocyte-macrophage interaction. Nylon wool column-enriched T lymphocytes from infected mice activate macrophages for antileishmanial effects; treatment of lymphocytes with anti-Thy-1.2 antibody plus complement abolishes this capacity. Furthermore, treatment with anti-Lyt-1 antibody plus complement (but not with anti-Lyt-2 plus complement) likewise abolishes the effector capacity of the lymphocytes. Parallel studies reveal that the percentage of Lyt-1+2- cells present in draining lymph nodes increases during the course of infection and reaches a peak with the onset of spontaneous resolution of the infection. Syngeneic, but not allogeneic, combinations of lymphocytes and infected macrophages result in macrophage activation. Furthermore, treatment of cells with appropriate anti-Ia monoclonal antibody abrogates the antileishmanial effects. These results indicate that Lyt-1+2- lymphocytes obtained from mice with spontaneously healing L. tropica infections can exert antileishmanial effects in vitro. This effect is genetically restricted--most likely to the I region of the MHC--and requires direct cell contact. The temporal relationship between the appearance of these effector lymphocytes in mice and the onset of disease resolution argues that they may also exert these antileishmanial effects in vivo.

Animals↗
PubMed1984

Effector cell analysis of tumor cell rejection in vivo in two syngeneic tumor systems exhibiting distinct in vitro cytotoxic mechanisms.

The nature of the in vivo anti-tumor effector cells was investigated in two different tumor system, MH134 hepatoma and X5563 plasmacytoma, in which tumor-specific antibodies and cytotoxic T lymphocytes (CTL), respectively, mediate in vitro tumor cell lyses. Winn assays utilizing MH134- and X5563-immune spleen cells revealed that in both tumor systems, tumor neutralization was produced exclusively by a tumor-specific immune Lyt-1 T cell subpopulation which was depleted of antibody-producing B cells or T cell subset(s) capable of generating CTL responses. These Lyt-1 T cells could exert their in vivo tumor-protective function under conditions in which MH134 tumor-specific antibody was not detected or in T cell-depleted recipient mice (B cell mice) in which CTL precursors were not recruited, indicating that their activities do not depend on the induction of antibody or CTL response. These results are discussed in the context of the relationships (1) between effector systems detected in in vitro cytotoxicity tests and effector mechanisms responsible for in vivo tumor protection, and (2) between epitopes or molecules required for triggering in vitro and in vivo effectors against the tumor.

Animals↗