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Biomedical subjects

E Kedar

Publications and source records attributed to E Kedar.

At least 37 records · Page 2Linked to original sources
PubMed1992

Chemo-adoptive immunotherapy of nude mice implanted with human colorectal carcinoma and melanoma cell lines.

The antitumor effects of chemotherapy, recombinant human interleukin-2 (IL-2), recombinant human interferon alpha A/D (IFN alpha), allogeneic human lymphokine-activated killer (LAK) cells, and antitumor monoclonal antibody (mAb), administered alone and in various combinations, were tested in athymic nude mice carrying human tumor xenografts. Treatment began 6-18 days after i.v. or i.p. inoculation of colorectal carcinoma or melanoma cell lines, when macroscopic growths were evident. Chemotherapy consisted of two or three courses of 5-fluorouracil (5-FU) or dacarbazine. IL-2 and/or IFN alpha were administered three to five times weekly for 1-3 weeks, usually starting 2-5 days after chemotherapy. Human LAK cells were infused once or twice weekly for 2 or 3 weeks concurrently with IL-2. In some experiments, murine anticolorectal carcinoma mAb (SF25) was administered. In both tumor systems, chemotherapy alone or immunotherapy alone (IL-2, IL-2 + LAK cells, IFN alpha, IL-2 + IFN alpha +/- LAK cells) had little or no therapeutic effects. Additive effects were obtained by combining chemotherapy with IL-2 and LAK cells or with IL-2 and IFN alpha. In the majority of the experiments, the most effective combination was chemotherapy + IL-2 + IFN alpha + LAK cells. Treatment with mAb was beneficial in the colorectal carcinoma system when combined with 5-FU + IL-2 or 5-FU + IL-2 + IFN alpha. Homing experiments with radiolabeled human and mouse LAK cells injected i.v. showed increased early accumulation in the liver and lungs, whereas freshly explanted mouse splenocytes localized mostly in the spleen and liver. The tissue distribution pattern of human LAK cells was similar in normal and tumor-bearing mice (with lung metastases). These findings suggest that combination of chemotherapy with cytokines and LAK cells can be partially effective for advanced solid human tumors even in the absence of the host's T-cell immune response. Preliminary experiments showed that tumor-specific, anti-melanoma T-cell clones were effective in local (s.c.) tumor growth inhibition (Winn assay) following coinjection with the autologous tumor cells.

Animals↗
PubMed1992

Narcotic-induced suppression of natural killer cell activity in ventilated and nonventilated rats.

Surgical stress and general anesthesia can suppress immune function and thus may increase postsurgical infections and tumor metastasis. We previously reported that two narcotics commonly used in high-dose opiate anesthesia (fentanyl and sufentanil) suppress natural killer (NK) cell activity in rats. Such doses of narcotics also cause respiratory depression accompanied by hypoxia, hypercarbia, and acidosis, which might account for the observed narcotic-induced NK suppression. In the present study, we compared the effects of fentanyl on NK activity in ventilated and non-ventilated rats. Fentanyl significantly suppressed NK cell activity to the same magnitude in the two groups, although the groups significantly differed in CO2 and O2 levels. The fact that high-dose fentanyl-induced NK suppression can be demonstrated in ventilated rats accentuates the relevance of these findings to clinical studies showing NK suppression in the immediate postoperative period. Such immunosuppression could be a risk factor for patients undergoing surgery, especially in cancer-related operations.

Animals↗
PubMed1992

Chemo-immunotherapy in patients with metastatic melanoma using sequential treatment with dacarbazine and recombinant human interleukin-2: evaluation of hematologic and immunologic parameters and correlation with clinical response.

We have treated 18 patients with metastatic malignant melanoma (MM) with high-dose IL-2 administered by continuous iv infusion in combination with dacarbazine (DTIC), and correlated the clinical response with various hematologic and immunologic parameters. Two regimens differing in the sequence of treatment were employed, and 1-6 treatment cycles were given, depending on patient response. Two patients had a complete response (CR, 46+m, 14m), two patients a partial response (PR, 16m,6m), one a minimal response and four had a stable disease lasting 2-7 months, thus the response rate (CR+PR) was 22%. None of the following parameters, tested prior to initiation of the therapy and 1-2 days after termination of each course of IL-2, correlated with the clinical response: WBC counts (total and differential), levels of blood CD4 and CD8 T cells, NK cells, monocytes and B cells, production of IL-1 and IL-1 inhibitor by monocytes, responsiveness to 3 mitogens, NK/LAK cell activity, and serum levels of IL-1 alpha, IL-2, soluble IL-2 receptor, and TNF alpha. The only prognostic parameter was the greater increase in the level of IL-2 receptor (Tac)-bearing lymphocytes in the responding patients after 1-3 cycles of IL-2. The data suggests that non-specific immune parameters have no prognostic value for patients undergoing IL-2-based immunotherapy.

Adolescent↗
PubMed1992

Cytokine-induced resistance to microbial infections in normal, immunosuppressed and bone marrow transplanted mice.

We studied the efficacy of in vivo and in vitro treatments with IL-1, IL-2, IL-3, and GM-CSF in the protection against bacterial (Salmonella typhimurium), fungal (Candida albicans) and viral (influenza virus A/PR8) infections, of normal, sublethally irradiated and lethally irradiated, bone marrow (BM) reconstituted mice. In parallel, the cytokines were tested for their ability to potentiate hematopoietic activity in vitro and in vivo. We demonstrate that, under the experimental conditions employed, IL-1 had the best protective activity against the three micro-organisms in both normal and immunocompromised mice when administered in vivo. Administration of IL-2 led to increased resistance in normal but not in immunodeficient mice, whereas GM-CSF had no beneficial effects. In contrast, preincubation of BM cells in these cytokines, singly or combined, prior to transplantation to lethally irradiated mice, did not confer protection against subsequent infection, although it increased the number of BM derived CFU-GM in culture (except in the case of IL-2). Administration of IL-1 or GM-CSF to BM transplanted mice facilitated WBC recovery, whereas IL-2 delayed it. Collectively, the data suggest that IL-1, alone or combined with other cytokines, may be beneficial in the prevention or treatment of microbial infections in immunocompromised and BM transplanted patients. It can also be concluded that enhanced hematopoietic recovery may not always coincide with the development of resistance to micro-organisms.

Animals↗
PubMed1991

Use of recombinant human interleukin-2 in conjunction with syngeneic bone marrow transplantation in mice as a model for control of minimal residual disease in malignant hematologic disorders.

Unlike allogeneic bone marrow transplantation (BMT), autologous BMT is not accompanied by immune-mediated graft-versus-leukemia (GVL) effects; hence, the relapse rate observed after autologous BMT in malignant hematologic disorders is higher than that observed after allogeneic BMT. Autologous BMT represents a much safer medical procedure available for many patients in need in situations where allogeneic BMT is not feasible or risky. The present experiments were designed to investigate whether it might be possible to combine the therapeutic benefits of autologous BMT with additional immunotherapy after BMT. The tumor model used for investigating GVL effects was the murine B-cell leukemia (BCL1), a spontaneous, nonimmunogenic, highly lethal leukemia of BALB/c origin. BALB/c mice inoculated with 10(3) BCL1 leukemia cells were treated on day-1 with cyclophosphamide 100 mg/kg and transplanted with normal syngeneic BM cells on day 0. High-dose recombinant interleukin-2 (rIL-2) (100,000 Cetus units x 3/day intraperitoneally x 5 consecutive days) was initiated on day +1, +7, or +21 after BMT. Kinetics of lymphocyte reconstitution after syngeneic BMT indicated a steep increase in the absolute number of peripheral blood lymphocytes on days 17 through 24. All experimental groups were observed for relapse. Mice receiving no rIL-2 therapy relapsed and died within 50 days after BMT, whereas mice receiving rIL-2 showed long-term disease-free survival. Optimal time for administration of rIL-2 was noted at 3 weeks post-BMT, with 90% of the mice surviving with no evidence of disease for more than 1 year. Similarly, when 10(4) BCL1 cells were given 1 day after syngeneic BMT to simulate minimal residual disease after syngeneic BMT, rIL-2 therapy administered at 14 days post-BMT seemed effective in prolonging disease-free survival in contrast to the same regimen given at 1 day after BMT. Our data suggest that immunotherapy with rIL-2 should be further investigated as a new immunotherapeutic tool for decreasing the relapse rate after BMT for hematologic malignancies.

Animals↗
PubMed1991

A short human and mouse MLR assay utilizing lymphokine (IL-2, IL-3) secretion as an early activation event.

The mixed leukocyte reaction is the only functional in vitro assay currently employed for confirmation of MHC matching between bone marrow recipients and their prospective donors and for MHC class II (HLA-Dw) typing. This assay is, however, time-consuming (6 days for human MLR), whereas for clinical purposes results are often required much earlier. In an attempt to shorten the MLR incubation period, we tested IL-2 (in human MLR) and IL-2/IL-3 (in mouse MLR) production as an indication of early stages of T cell activation. We here describe a shorter assay in which IL-2 and IL-3 secretion during MLR was assessed by adding the respective lymphokine-dependent cell lines either to the MLR supernatants or directly to the original MLR cultures, using the colorimetric (3-[4,5 Dimethylthiazol-2-yl]-2.5-diphenyltetrazolium bromide) (MTT) technique or the 3H-thymidine incorporation assay. In both human and mouse MLR systems, lymphokine production peaked at 24-48 hr after culture initiation, allowing tests to be completed within 48 to 72 hr. Weak MLR responses, as detected by lymphokine production, could be considerably amplified by irradiating (250-1000 cGy) the responder cells and by adding heparin (1-10 U/ml) to the cultures. The results obtained by this novel procedure correlated with those obtained by the standard 6-day human MLR assay in over 250 combinations tested thus far, and therefore it may replace the standard MLR procedure.

Animals↗
PubMed1990

Cytotoxic T lymphocytes reactive against a syngeneic murine tumor and their specific suppressor T cells are both elicited by in vitro allosensitization.

Sensitization of C57BL/6 (B6, H-2b) splenocytes against normal BALB/c (H-2d) leukocytes (B6 a/BALB) in bulk MLC induced CTL reactive against the syngeneic (H-2b) nonimmunogenic lymphoma PIR-2, in addition to the CTL directed against the corresponding (H-2d) allotargets. However, MLC-derived lymphocytes did not directly exhibit anti-PIR-2 cytotoxicity in spite of the high anti-PIR-2 CTL frequency (up to 1/20) among them, as demonstrated by the limiting dilution culture (LDC) technique. The present study was undertaken to resolve this contradiction. We found that anti-PIR-2 cytotoxicity could be detected only when B6 a/BALB MLC-derived responding cells were plated in LDC at low numbers (less than 200) of cells/well. In contrast, increasing the number of the plated cells to 500-5,000 resulted in a gradual decrease in the percentage of wells cytotoxically reactive against PIR-2, whereas the percentage of wells exhibiting cytotoxicity against the allotargets remained unchanged (100%). This decrease of anti-PIR-2 cytotoxicity in LDC and the lack of anti-PIR-2 reactivity among MLC-derived lymphocytes were shown by mixing experiments to result from the activity of radioresistant Thy-1+, Lyt-2+, L3T4- suppressor cells, blocking the anti-PIR-2 cytotoxicity at the effector phase. The suppression was specific as indicated by the following observations: (a) freshly obtained B6 splenocytes, cultured unsensitized B6 splenocytes, mitogen-induced B6 lymphoblasts, B6 LAK cells, or B6 a/B6 MLC-derived lymphocytes were not suppressive; (b) anti-PIR-2 cytotoxicity elicited in B6 a/BALB LDC was suppressed only by lymphocytes derived from B6 a/BALB MLC and not from B6 a/C3H (H-2k) MLC; and (c) B6 a/BALB MLC-induced suppressor cells could be adsorbed on monolayers of BALB/c but not of C3H lymphoblasts. Since both syngeneic tumor and allogeneic target cells were lysed by the same clonal cell population but only the antisyngeneic activity was suppressed, we suggest that a single CTL can exhibit two cytotoxic activities that are differentially affected by the described suppressor cells. This mode of suppression may play a role in controlling autoimmune reactivity.

Animals↗
PubMed1990

Selective accumulation of lymphocyte precursor cells mediated by stromal cells of hemopoietic origin.

Thymocytes were propagated in long-term cultures supported by stromal cells of both bone marrow and thymus origin. Interleukin 2 (IL-2) supplementation augmented the cell yield and allowed detailed phenotype analysis. Within 2-3 months of culture a cell population was selected in which the expression of Thy-1 antigen persisted, CD4 and CD8 antigens gradually declined, and Pgp-1 antigen, found on less than 5% of fresh thymocytes, was strongly increased. This cultured cell population (Thy-1.2 origin) contained no detectable spleen colony-forming units (CFU-S) but efficiently repopulated the thymus of Thy-1.1-irradiated congenic mice, indicating the precursor T-cell nature of the population. Upon removal from the stroma, the T cells exhibited poor cytotoxicity towards syngeneic tumor cells. Further propagation with IL-2 in the absence of stroma resulted in the acquisition of cytotoxic ability. Replacement of the horse serum used in the above experiments with fetal calf serum resulted in accumulation of cells expressing B220 antigen. This experimental model provides the means to maintain lymphocyte precursor cells in long-term culture and to further study their differentiation in the absence of stroma, both in vitro and in vivo.

Animals↗
PubMed1990

IL-2 activated cell-mediated immunotherapy: control of minimal residual disease in malignant disorders by allogeneic lymphocytes and IL-2.

The present experiments were designed to investigate whether it might be possible to combine their therapeutic benefits of autologous BMT and allogeneic BMT following administration of T-lymphocyte depleted marrow allografts with additional immunotherapy following BMT. The tumor model used for investigating graft vs leukemia (GVL) effects was the murine B-cell leukemia (BCL1), a spontaneous, nonimmunogenic, highly lethal leukemia of BALB/c origin. Immunotherapy with high dose recombinant human interleukin-2 (IL2) (10(5) Cetus units x 3/day intraperitoneally (IP) for 5 days) produced significant anti-tumor effects in BCL1-bearing mice. BALB/c mice inoculated with 10(3) BCL1 leukemia cells received were treated on day -1 with cyclophosphamide 100 mg/kg and transplanted with normal syngenic BM cells on day 0. High-dose IL2 (100,000 Cetus Units x 3/day IP x 5 consecutive days) was initiated on day +1, +7, or +21 following BMT. Optimal time for administration of IL2 was noted at 3 weeks post-BMT with 90% of the mice surviving with no evidence of disease greater than 1 year. An experimental model designed to study GVL effects in a state of minimal residual disease following T-cell depleted allogeneic BMT indicated that mice receiving low dose of BCL1 challenge (10(4] were successfully treated by either IL2 (2 x 10(4) Cetus units x 2/day IP x 3 days), allogeneic spleen cells (10(6) on day +1, 10(7) on day +5 and 5 x 10(7) on day +9) alone and certainly following a combination of both.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Allosensitization in IL-2-containing limiting dilution cultures generates cytotoxic T lymphocytes (CTL) rather than LAK cells reactive with a syngeneic nonimmunogenic murine tumor.

We have previously demonstrated that high frequency (1/20) of potent cytotoxic cells reactive with the nonimmunogenic lymphoma PIR-2 of C57BL/6 (B6, H-2b) origin, can be obtained by allosensitization of syngeneic B6 splenocytes against BALB/c (H-2d) splenocytes in limiting dilution cultures (LDC). Since a high concentration (250 U/ml) of exogenous interleukin 2 (IL-2), sufficient for the elicitation of lymphokine-activated killer (LAK) cells, was used in the LDC, and because the LDC-derived cytotoxic cells were active against a wide spectrum of target cells, we investigated whether the anti PIR-2 effector cells are LAK cells or cytotoxic T lymphocytes (CTL). We found that depletion from the B6 responder cell population of Lyt2+ (CTL precursors), but not of asialo GM1+ (LAK cell precursors), prior to LDC, results in the ablation of anti PIR-2 activity. When B6 splenocytes were plated in LDC with IL-2, in the absence of allogeneic stimulating cells, the resulting anti PIR-2 activity was greater than 10- to 500-fold lower than that obtained in LDC in the presence of allogeneic stimulating cells and IL-2. These and other observations suggest that the cytotoxic response against syngeneic tumors elicited by alloantigens in LDC is mediated by CTL rather than LAK cells, and that allogeneic sensitization in LDC can provide a means for the generation of CTL against syngeneic, nonimmunogenic tumors.

Animals↗
PubMed1989

Chemo-immunotherapy of murine tumors using interleukin-2 (IL-2) and cyclophosphamide. IL-2 can facilitate or inhibit tumor growth depending on the sequence of treatment and the tumor type.

The antitumor effect of interleukin-2 (IL-2), alone and in combination with cyclophosphamide was assessed in mice with established sarcoma (MCA 105, H-2b), carcinoma (M109, H-2d) and T lymphoma (PIR-2, H-2b). Whereas administration of IL-2 alone (5 x 10(4)-10 x 10(4) U, i.p. twice daily, for 4-8 consecutive days) prolonged the survival of mice with the solid neoplasms, it enhanced tumor growth and decreased survival of mice with the lymphoma. In the PIR-2 lymphoma, no IL-2 receptor (TAC) could be detected, nor could we demonstrate IL-2 tumor growth stimulation in vitro. A synergistic therapeutic effect was achieved in mice with the solid tumors, but not in mice with the lymphoma, only when IL-2 was given 1-4 days after cyclophosphamide (100-200 mg/kg). Conversely, administration of IL-2 1-4 days prior to cyclophosphamide resulted, in all three tumor systems, in enhanced tumor growth and in decreased survival as compared with mice receiving cyclophosphamide alone. Similarly, treatment with IL-2 both before and after cyclophosphamide was less efficacious than a single course of IL-2 given afterwards. It is concluded that for maximal therapeutic efficacy, IL-2 should be administered following chemotherapy, and that certain tumors may respond adversely to IL-2 treatment.

Adjuvants, Immunologic↗
PubMed1989

The use of recombinant cytokines for enhancing immunohematopoietic reconstitution following bone marrow transplantation. I. Effects of in vitro culturing with IL-3 and GM-CSF on human and mouse bone marrow cells purged with mafosfamide (ASTA-Z).

Enhanced colony formation (CFU-GM) in vitro was observed in murine and human bone marrow (BM) cells following pre-incubation for 2-3 days with recombinant murine GM-CSF or natural purified murine IL-3, and recombinant human GM-CSF or IL-3, respectively. Pre-incubation in the presence of both GM-CSF and IL-3 produced additive stimulatory effects. BM cells previously treated in vitro with mafosfamide (ASTA-Z) under conditions identical to those used in the purging of autologous BM grafts, also demonstrated an enhanced cumulative response to combinations of GM-CSF and IL-3, with up to 100-fold increase in CFU-GM as compared with controls (p less than 0.001). In mice, the number of CFU-S was also significantly increased (2-20 times) following incubation of unpurged and purged BM cells in murine IL-3 and/or GM-CSF. Interestingly, the frequency of both CFU-GM and CFU-S in BM cells first purged with ASTA-Z and then cultured with both cytokines was significantly higher (p less than 0.01) than that in fresh, intact BM cells. In addition, mice transplanted with unpurged or purged, cytokine cultured syngeneic BM cells exhibited a significantly (p less than 0.01) earlier reconstitution of peripheral white blood cells and of BM CFU-GM, and a significantly enhanced anti-sheep red blood cell plaque-forming cell response. Overall, the data suggest that it might be possible to enhance immunohematopoietic reconstitution in recipients of unmanipulated, as well as ASTA-Z purged autologous BM following short-term culture of BM cells with recombinant colony stimulating factors prior to bone marrow transplantation.

Animals↗
PubMed1988

Typing of HLA class II and class I antigens using PHA-activated, IL-2-propagated T lymphocytes.

We describe here a simple procedure, by which HLA class II antigens can be accurately and reliably identified in those patients where there is minimal or absent expression of HLA-DR,DQw antigens on B cells, or when the total number of leukocytes recovered from the patients do not permit reliable typing. Ficoll-Hypaque-separated peripheral blood mononuclear leukocytes, fresh or cryopreserved, were activated by PHA and then propagated in IL-2-containing medium until enough cells for typing were obtained (usually 7-14 days). At this stage, the cultured cells were shown to be primarily T cells (greater than 90% CD3+). Since the activated T cells propagate in the presence of IL-2, even a small number (10(4] of fresh or cryopreserved patients' cells suffice for this protocol. To date we have been able to successfully HLA-DR,DQw type 34/34 bone marrow transplantation candidates and 12/12 long-term dialysis patients, who were untypable using fresh cells. HLA-DR,DQw antigens on activated T cells from normal individuals were identical to those found on their uncultured B cells. In addition, class I antigens that were undetectable on the uncultured cells of one patient could be identified on activated T cells. The HLA antigens identified on the patients' activated T cells were confirmed by phenotypic analysis of cells from family members.

B-Lymphocytes↗
PubMed1988

Lysis of murine macrophages infected with intracellular pathogens by interleukin 2-activated killer (LAK) cells in vitro.

To determine if murine lymphocytes activated by interleukin 2 (IL-2) were cytotoxic against syngeneic elicited peritoneal macrophages (M phi) infected with intracellular pathogens, splenocytes that had been cultured with IL-2 for 5 or 10 days were studied in vitro. These cells, [lymphokine-activated killer (LAK) cells] showed significantly greater cytotoxicity against M phi infected with Leishmania major or Legionella pneumophila than against uninfected M phi. Preferential cytotoxicity against infected M phi was best shown using effector-to-target-cell ratios of 1:1-20:1; when ratios greater than or equal to 40:1 were employed, uninfected M phi were also lysed. The extent to which M phi that had been incubated with L. major were lysed depended upon the proportion of M phi containing intracellular organisms. After infection with L. major, the duration of incubation did not appear to influence the degree of lysis by LAK cells.

Animals↗
PubMed1988

Current problems and future goals in clinical bone marrow transplantation.

Allogeneic bone marrow transplantation (BMT) is associated with the cumulative toxicity of high dose chemotherapy and/or radiation therapy regimens currently in use, with acute and chronic graft vs host disease (GVHD), as well as with the consequences of delayed immunological reconstitution due to slow maturation of the immune system and drugs currently used for prevention of GVHD. Although GVHD may be overcome by T-cell depletion it leads to an increased incidence of graft rejection and relapse of the original malignancy. These too represent major problems. Autologous BMT results in high relapse rates due to lack of immune-mediated allogeneic interactions of grafted cells against tumor cells of the host. In view of the fact that experiments in animal models of human disease suggest that antileukemic effects of allogeneic marrow grafts may be partially independent of GVHD, new approaches for amplification of antitumor effects of autologous and allogeneic cells by cytokines and by lymphokine-activated cells are discussed. Evidence for antileukemia effects of IL-2 therapy in animals is presented. Beneficial effects of several cytokines in autologous and allogeneic BMT are suggested by significant facilitation of immunological and hematopoietic reconstitution following transplantation of bone marrow cells treated in vitro with cytokines (including ASTA-Z-purged marrow) and following in vivo administration of cytokines in conjunction with BMT. Overall, in view of several innovative biological interventions, it seems that significant progress in autologous and allogeneic BMT may be underway; the concept yet to be established is that successful and less risky BMT may be accomplished by replacing aggressive chemoradiotherapy regimens with sophisticated immunomanipulations and biological response modifying agents.

Animals↗
PubMed1988

Immunomodulating effects in vitro of interleukin-2 and interferon-gamma on human blood and bone marrow mononuclear cells.

Mononuclear cells (MNC) derived from peripheral blood (PBMNC) of 23 normal donors and 4 AIDS patients, and from bone marrow (BMMNC) of 15 normal donors were incubated at 37 degrees C in culture medium alone or in the presence of either natural or recombinant human interleukin-2 (IL-2) or recombinant human interferon-gamma (IFN-gamma; 1-1,000 U/ml). The cultured cells were washed on days 1, 4 or 7 and tested for various immune functions in vitro and for cell surface phenotype. IL-2, but not IFN-gamma, was found mitogenic for both PBMNC and BMMNC. The natural killer (NK) activity of both PBMNC and BMMNC was the only function tested that was markedly augmented (over 100-fold compared to medium control) by both lymphokines. Pretreatment of PBMNC with IL-2 at greater than or equal to 10 U/ml profoundly suppressed (up to 90%) various functions, such as mitogenic responses (phytohemmagglutinin, concanavalin A, pokeweed mitogen), allogeneic mixed leukocyte reaction, antibody production and T cell colony formation in agar. In contrast, some BMMNC functions were elevated at low doses of IL-2 and IFN-gamma, and significant suppression of BMMNC was seen only with high doses of IL-2 (greater than or equal to 100 U/ml) and IFN-gamma (1,000 U/ml). IL-2 was by far more effective than IFN-gamma in both the amplification of NK activity and the suppression of most of the other functions. IL-2, but not IFN-gamma, was found to activate/induce suppressor cells and increased the proportion of Leu-2+ (CD8) cells in PBMNC; the suppressive effect was time- and dose-dependent. The IL-2-induced suppression could be diminished by inclusion of anti-IL-2 antibody during the pretreatment phase. Similar suppressive effects were noted in PBMNC from AIDS patients. These findings suggest that: (a) high-dose IL-2 may elicit immunosuppression which can be mediated by nondiscriminative highly cytotoxic cells (i.e. lymphokine-activated killer cells) and/or by noncytotoxic, nonspecific suppressor cells, and (b) that PBMNC respond differently to the lymphokines than do BMMNC.

Acquired Immunodeficiency Syndrome↗