Biomedical subjects

N Hozumi

Publications and source records attributed to N Hozumi.

At least 37 records · Page 2Linked to original sources

PubMed1997

Human gene therapy.

Human gene therapy and its application for the treatment of human genetic disorders, such as cystic fibrosis, cancer, and other diseases, are discussed. Gene therapy is a technique in which a functioning gene is inserted into a human cell to correct a genetic error or to introduce a new function to the cell. Many methods, including retroviral vectors and non-viral vectors, have been developed for both ex vivo and in vivo gene transfer into cells. Vectors need to be developed that efficiently transfer genes to target cells, and promoter systems are required that regulate gene expression according to physiologic needs of the host cell. There are several safety and ethical issues related to manipulating the human genome that need to be resolved. Current gene therapy efforts focus on gene insertion into somatic cells only. Gene therapy has potential for the effective treatment of genetic disorders, and gene transfer techniques are being used for basic research, for example, in cancer, to examine the underlying mechanism of disease. There are still many technical obstacles to be overcome before human gene therapy can become a routine procedure. The current human genome project provides the sequences of a vast number of human genes, leading to the identification, characterization, and understanding of genes that are responsible for many human diseases.

Genetic Diseases, Inborn↗

PubMed1996

Multiple levels of regulation for self-tolerance in beef insulin transgenic mice.

To characterize the mechanism(s) of tolerance toward soluble self-antigens (Ags), beef insulin (BI) transgenic (Tg) mice were generated in which the transgene was expressed in pancreatic beta-cells. Our previous data showed that: (i) Ag-specific tolerance can be induced and/or maintained in peripheral T cells in thymectomized BI-Tg mice and (ii) CD4+ Th2 regulatory T cells are involved in maintaining peripheral tolerance (by anti-BI antibody response). In this paper, we have further characterized the relationship of low levels of BI expression (10(-10)-10(-11) M) in Th1/Th2 activation. In addition, we have explored intrathymic events associated with tolerance to self-Ags not expressed in the thymus and/or to circulating self-Ags. Limiting dilution analysis showed that there was a significantly higher frequency of BI-specific Th2 cells in Tg mice with a corresponding higher frequency of Th1 cells in non-Tg mice. While there was no transgene expression in the thymus (by RT-PCR), independent studies showed that BI can be processed and presented in the Tg thymus, which correlated with the Ag-specific hyporesponsiveness of mature thymocyes detected in vitro. High-dose rIL-2 (150 U/ml) was able to restore in vitro peripheral T cell response of Tg mice to levels comparable to those of the non-Tg control. Collectively, our data suggest that: (i) there is a differential activation of BI-specific Th1/Th2 cells in vivo in the presence of low Ag concentration; (ii) the thymus may play a role in self-tolerance to Ags whose expression in adults is restricted to the periphery; and (iii) multiple levels of regulation such as thymic selection, peripheral anergy, and active suppression may be involved in tolerance to BI in BI-Tg mice.

Animals↗

PubMed1996

Human hematopoiesis in SCID mice implanted with human adult cancellous bone.

The persistence of hematopoietic cells from human adult cancellous bone fragments implanted subcutaneously into CB-17 scid/scid mice was studied. Recipient mice received either no pretreatment (control group) or pretreatment with 3 Gy total-body irradiation and anti-asialo GM1 sera (ASGM1; pretreated group) before implantation. Pretreated severe combined immunodeficient (SCID) mice implanted with human bone were subsequently given ASGM1 every 7 days for the duration of the experiments. At 12 weeks postimplantation, flow cytometry of cells from pretreated and control animal tissues detected human CD45+ cells in the mouse spleen (mean, 7.8% and 3.4% positive cells, pretreated and control animals, respectively), bone marrow (BM; mean, 16.5% and 4.8% positive cells, respectively), and blood (mean, 5.5% and < 2% positive cells, respectively), and in the implanted human bone (73% and 8.9% positive cells, respectively). At 12 weeks, pretreated mice had human granulocyte-macrophage colony-forming cells (GM-CFC) and burst-forming units-erythrocyte (BFU-E) in the implanted human bone in the murine BM and in some of the spleens. The spleens also had extensive infiltration of human B cells and macrophages. Mean serum levels of human IgG in pretreated animals were 14 micrograms/mL during weeks 6 to 12, compared with trace levels (< 1 microgram/mL) in control mice. Bone from patients with acute myeloblastic leukemia (AML) was also implanted in pretreated SCID mice, and retrieved at 8 weeks for analysis. Comparison of preimplantation and implanted samples showed that the original histology was maintained, and massive infiltration of human CD68+ cells was observed in the mice spleens and BM. Implantation of AML bone in SCID mice facilitates analysis of in situ AML cell interaction with stromal cells in the leukemic state, and therapies against AML can be tested in this system, especially the selective killing of AML cells in the presence of other BM cells. Furthermore, this model requires no exogenous administration of cytokines to maintain human hematopoiesis with both normal or AML bone. Because the structure and function of both normal and diseased human adult bone is maintained, this animal model should facilitate investigation of both normal human hematopoiesis and hematopoietic malignancies.

Acute Disease↗

PubMed1996

Tolerance is overcome in beef insulin-transgenic mice by activation of low-affinity autoreactive T cells.

To gain insight into the factors controlling the maintenance or loss of T cell self tolerance we produced beef insulin (BI)-transgenic BALB/c mice. Transgenic mice express BI under control of the human insulin promoter and secrete physiological amounts of beef insulin. Although these mice are tolerant to BI, as evidenced by the lack of insulin-specific IgG antibody production following intraperitoneal immunization, tolerance is not complete. Footpad immunization results in a weak antigen-specific T cell proliferative response, indicating the presence of self-reactive BI-specific T cell in the periphery. These T cells are functional in vivo, providing support for IgG1, IgG2a, and IgG2b BI-specific antibody production, but require higher higher concentrations of antigen than nontransgenic T cells (both in vivo and following recall responses in vitro) to become activated. In vitro, BI-specific T cell proliferation in BI-transgenic mice can be largely restored by addition of interleukin-2, indicating that a significant component of T cell tolerance is mediated by anergy. To characterize the autoreactive T cells that become activated when tolerance is broken, BI-specific T cell hybridomas were generated from transgenic mice and compared to a panel of hybridomas previously derived from nontransgenic BALB/c mice. The majority of BI-transgenic hybridomas recognized the immunodominant A1-14 beef insulin peptide but with lower avidity than BALB/c hybridomas. Consistent with this, none of the dominant T cell receptor rearrangements found in the BALB/c BI-specific T cell receptor repertoire were found in the transgenic hybridomas. These results indicate that, despite evidence for clonal inactivation of many BI-specific T cells in BI-transgenic mice, loss of tolerance results from activation of low-affinity antigen-specific T cells that appear to have escaped this process.

Amino Acid Sequence↗

PubMed1996

Expression of exogenous p59fyn modulates signaling in an immature B cell line, WEHI-231.

The WEHI-231 B lymphoma line is representative of immature B cells, which undergo growth arrest/apoptosis following cross-linking of surface immunoglobulin M (sIgM). In B cells, sIgM engagement has been shown to induce immediate (within seconds) activation of src family protein tyrosine kinases (PTKs) such as p53lyn/56lyn, p55blk, p56lck and p59fyn which are associated with B cell antigen receptor (BCR) complex. However, p59fyn expression is very low in both normal immature B cells and apoptosis-prone B cell lines, including WEHI-231. Such a finding prompted us to investigate the effects of ectopic expression of p59fyn in growth regulation of WEHI-231 cells. We have obtained WEHI-231 transfectants expressing the exogenous p59fyn by retroviral mediated gene transfer method. The transfectants demonstrated increased [Ca2+]i level in both the non-stimulated condition and sIgM cross-linking. The expression of ectopic p59fyn also increased the sensitivity of the transfectants to growth arrest signal by sIgM cross-linking. The results suggest that p59fyn can modulate signal transduction and growth regulation when expressed in the immature B cell line.

Animals↗

PubMed1996

Human osteoblasts survive and deposit new bone when human bone is implanted in SCID mouse.

We describe the first successful engraftment of viable human bone that maintains human osteoblast function and deposits new bone after implantation into pretreated SCID (Hu-bone-SCID) mice. The pretreatment consists of radiation before bone implantation and subsequent administration of antiasialo GM1 antisera every 7 days to deplete mouse macrophage and natural killer (NK) cell activity. The implanted bone samples were analyzed at various times up to 8 weeks. Comparison of pre- and post-implanted human specimens in untreated and pretreated SCID mice showed that while specimens underwent resorption and necrosis in untreated SCID mice, the structure of the implanted bone was preserved in the pretreated Hu-bone-SCID mice. In addition, histochemistry and histomorphometric analysis combined with tetracycline labeling showed that new bone formed in in the implants in the pretreated SCID mice. That the new bone resulted from the activity of the implanted human bone cells rather than from induction of differentiation of host mesenchymal cells into mouse osteoblasts was shown by immunohistochemical analysis with two different monoclonal antibodies (mAb), one mAb recognizing human HLA class II antigens and one recognizing human osteoblasts and osteocytes. Donor variability was observed in the implanted bone; however, bone from the same donor maintained its characteristics in all Hu-bone-SCID mice, and striking quantitative differences were seen in bone implanted from young (4-9 years) vs. adult (67-82 years) individuals. This model will be useful to investigate and compare endogenous osteoblast activity in different bone samples without the variables of isolating cells and examining them in vitro.

Aged↗

PubMed1996

The use of SCID mice in biotechnology and as a model for human disease.

The use of SCID (severe combined immunodeficient) mice in medical research and biotechnology has increased tremendously in recent years. This review outlines the major characteristics of these animals and the impediments that they pose to the engraftment of human cells and tissues. The development of our SCID mice pretreatment protocol (anti-asialo GM1 antisera and radiation) is described, and the results of xenotransplantation studies of human cells and tissues in these pretreated animals are outlined. Wherever possible, data from transplantation studies (of human tissues and cells) in pretreated and nonpretreated animals are compared. The potential of our pretreated SCID mice for medical research and biotechnology is discussed.

Animals↗

PubMed1996

Endogenous interleukin 6 can function as an in vivo growth- stimulatory factor for advanced-stage human melanoma cells.

We have previously shown that a majority of human melanoma cell lines derived from early-stage lesions were growth inhibited by exogenous interleukin 6 (IL-6) in vitro, whereas cell lines from advanced-stage lesions were resistant to such IL-6-induced growth inhibition. Among the resistant melanoma cell lines, 50-60% constitutively produced IL-6, which appeared to function as a growth stimulator in vitro, based on the growth-suppressive effects of antisense oligonucleotides to the IL-6 gene. The present study was primarily aimed at evaluating whether endogenous IL-6 also functions in vivo as a growth modulator for IL-6-producing and -nonproducing melanoma cells. To do so, we first introduced an IL-6 expression vector into IL-6-nonproducing human melanoma cells using WM35, an early-stage (radial growth phase) cell line, the growth of which is normally inhibited by IL-6, and WM983A, an advanced-stage cell line, the growth of which in vitro is not affected by exogenous IL-6. None of the IL-6-producing transfectants showed a significant alteration in tumor growth in nude mice. Next, two IL-6-producing melanoma cell lines, both of which were derived from metastases, MeWo and WM9, and which are growth resistant to exogenously added IL-6, were transfected with an antisense IL-6 expression vector. Several transfectant clones manifested a constitutive decrease in IL-6 gene expression and protein production, and they also gave rise to much smaller tumors with slower growth rates and longer latency periods. However, these IL-6 antisense transfectants were not growth suppressed in in vitro cell cultures, relative to their respective parental controls. Taken together, the results demonstrate that endogenous IL-6 can indeed function as a growth stimulator for human cutaneous melanomas in vivo. This growth-stimulatory or survival mechanism remains to be clarified but may be paracrine rather than autocrine in nature.

Animals↗

PubMed1995

Interleukin 12 in combination with anti-interleukin 10 reverses graft prolongation after portal venous immunization.

Portal venous pretransplantation transfusion augments allogeneic skin graft survival in mice transplanted across multiple minor histocompatibility barriers. We have shown in earlier studies that this is correlated with preferential activation for production of type-2 cytokines (interleukin [IL]-4 and IL-10) and decreased production of type-1 cytokines (IL-2 and interferon-gamma). We show that recombinant IL-12, in association with anti-IL-10 monoclonal antibody, can reverse in vivo the graft prolongation afforded by portal venous immunization and the altered cytokine production that follows. These alterations are in turn associated with increased expression of messenger RNA for interferon-gamma, IL-2, and IL-12 and decreased expression of IL-4, IL-10, and IL-13, as determined by non-quantitative polymerase chain reaction using cells obtained from lymph nodes draining the graft. Recombinant IL-12 in vitro also produces dose-related inhibition of activation for production of type-2 cytokines.

Animals↗

PubMed1995

A human model of xenogeneic graft-versus-host disease in SCID mice engrafted with human peripheral blood lymphocytes.

Despite previous attempts there is currently no suitable animal model available for xenogeneic graft versus host disease (XGVHD) mediated via human immunocompetent cells. Recently, we have developed an efficient protocol to engraft SCID mice with human peripheral blood lymphocytes (Hu-PBLs). The engraftment efficiency is extremely high, such that 100% of Hu-PBL-SCID mice die of XGVHD within 4 weeks after engraftment with Hu-PBLs (3-5 x 10(7) cells). A series of experiments was performed to investigate the mechanisms involved in the severe XGVHD. The results suggest that XGVHD was induced by human CD4+ T cells, antixenogeneic (antimouse) antibodies, and lymphokines. The SCID mouse model will be extremely valuable for the evaluation and development of immunosuppressive agents and transplantation protocols for human XGVHD.

Animals↗

PubMed1995

Antigen receptor-triggered apoptosis in immature B cell lines is associated with the binding of a 44-kDa phosphoprotein to the PTP1C tyrosine phosphatase.

While cross-linking of the membrane IgM (mIgM) molecules expressed on WEHI 231 lymphoma cells induces these cells to undergo apoptosis, we have previously observed that ligation of the mIgD expressed on IgD-transfected WEHI 231 (W delta) cells is not associated with induction of cell death. Thus mIgM+IgD+ W delta cells provide a valuable reagent for delineating the molecular events which modulate the physiologic outcome of B cell antigen receptor (BCR) engagement. In view of recent data implicating the cytosolic phosphotyrosine phosphatase PTP1C in the regulation of BCR signaling capacity, we used W delta cells to investigate the potential role for PTP1C in modulating the cell response to BCR activation. The results of this analysis revealed PTP1C to undergo rapid tyrosine phosphorylation following mIgM or mIgD cross-linking and to associate with a number of other phosphoproteins in stimulated W delta cells. Among these latter phosphoproteins, one prominent species of about 44 kDa (pp44) which co-precipitated with PTP1C in mIgM-ligated cells was not detected in PTP1C immunoprecipitates from mIgD-ligated cells. The association of PTP1C with this 44-kDa phosphoprotein following mIgM cross-linking was also observed in two additional B cell lines representing an immature state of differentiation, but was not detected after BCR engagement in two representative mature B cell lines or in splenic B cells. Initial data concerning the identity of pp44 indicate that this molecule does not represent the Shc, MAPK or Ig-beta proteins and may, therefore, constitute a previously unidentified signaling effector. While the structural and biochemical properties of pp44 require further definition, the findings suggest that BCR-triggered interactions of PTP1C with pp44 occur only in the context of an immature state of cellular differentiation and the induction of apoptosis. These data therefore suggest that PTP1C interactions with pp44 may be relevant to the transduction of BCR signals which evoke cell death.

Animals↗

PubMed1995

Evidence for Th2 cell-mediated suppression of antibody responses in transgenic, beef insulin-tolerant mice.

Clonal deletion, anergy and suppression have all been considered mechanisms of immunological tolerance. Although adoptive transfer of immunosuppression has been shown to occur in the periphery, particularly for transplantation tolerance, it has proven difficult to characterize this phenomenon further, due to the lack of suppressor T cell clones. To characterize tolerance towards a physiological soluble antigen, we constructed beef insulin (BI) transgenic (Tg) BALB/c (H-2d) mice, in which the BI transgene is expressed in pancreatic beta cells. These Tg mice were tolerant to BI immunization at the level of both humoral and cell-mediated immune responses. Adoptive transfer of splenocytes from Tg mice into normal syngeneic BALB/c mice demonstrated that the reduction in antibody production is regulated by transferred T cells. The cytokine profile of T cell clones obtained after selection in vitro demonstrated dominant Th1 clones from normal non-Tg mice and dominant Th2 clones from Tg mice. Some Th2 clones (CD4+) from Tg mice produced significant suppression of antibody production after adoptive transfer into normal syngeneic BALB/c mice. These data confirm the existence of Th2 regulatory T cells in vivo in a model of peripheral tolerance to a physiological soluble antigen as a potential mechanism for self tolerance.

Animals↗

PubMed1995

Both MHC and background gene heterozygosity alter T cell receptor repertoire selection in an antigen-specific response.

Many autoimmune diseases are associated with specific class II MHC alleles; however, this association is not complete. One explanation for the variable expression of disease in susceptible individuals is that variability in the TCR repertoire may alter the potential to generate pathogenic autoreactive T cells. The current study was undertaken to examine the possibility that MHC and background heterozygosity, which is the norm in the outbred human population, alters the expressed TCR repertoire and, if so, whether this has an impact on peptide recognition and antigenic specificity. We, therefore, systematically analysed the beef insulin-specific TCR repertoire in inbred BALB/c mice before and after introduction of MHC heterozygosity (BALB/c x BALB.K)F1 mice, or MHC and background gene heterozygosity (BALB/c x A/J)F1 mice. We show that T cells from all three repertoires are predominantly Ad-restricted and recognize the same immunodominant peptide. Despite this, the beef insulin-specific TCR repertoires in F1 mice differ from those seen in BALB/c mice with the most dramatic changes seen in (BALB/c x A/J)F1 mice. These changes are accompanied by subtle differences in the antigenic specificity of the T cells. The results demonstrate that both MHC and background gene heterozygosity affect TCR repertoire selection, suggesting that the variable expression of autoimmune disease in individuals with a susceptible MHC allele may result, in part, from variability in the TCR repertoire introduced by this heterozygosity.

Amino Acid Sequence↗

PubMed1995

Effect of Mycoplasma arthritidis superantigen on enzymatically induced arthritis in mice.

The objective of this study was to examine the effect of the stimulation of the immune system with Mycoplasma arthritidis superantigen (MAS) on joint inflammation and cartilage destruction. MAS was administered either alone or combined with a model of degenerative arthritis induced by intraarticular injection of collagenase enzyme. Intraperitoneal injection of MAS resulted in activation of peripheral lymphocytes in BALB/c mice, as shown by a proliferative response of splenocytes isolated from MAS-treated animals to IL-2-containing supernatant. Intraperitoneal or intra-articular administration of MAS alone at concentrations maximally activating lymphocytes had no detectable effect on joints. Intra-articular injection of collagenase resulted in some infiltration of inflammatory cells into the joints, hyperplasia and hypertrophy of synovial lining, pannus formation and surface loss of proteoglycans 7 days following the injection. At 21 days, the animals showed almost total loss of cartilage and minimal or no inflammation. Animals receiving MAS in addition to collagenase treatment showed similar changes in the joints. These data have demonstrated that activation of the immune system with MAS in vivo does not increase joint inflammation or cartilage degradation in enzymatically induced arthritis.

Animals↗

PubMed1994

Conserved amino acid residues in the complementarity-determining region 1 of the TCR beta-chain are involved in the recognition of conventional Ag and Mls-1 superantigen.

Superantigens activate T cells by interacting primarily with the V beta region of the TCR. This report describes a series of studies performed to elucidate the role of the conserved amino acid motif (Asp-His-Asn) in the complementarity-determining region 1 (CDR1) of the TCR V beta chains that recognize murine endogenous superantigen Mls-1. By using site-directed mutagenesis of the Mls-1-reactive TCR V beta 6 gene, it is shown that the alterations of the conserved CDR1 motif disrupt Mls-1 superantigen and conventional Ag recognition in vitro. The loss of V beta 6 (mutant)+ TCR reactivity to Mls-1 superantigen is apparently dependent on the partner alpha-chain in the V beta 6/V alpha 3 TCR pairing shows some reactivity to Mls-1, whereas other TCR pairings do not. The examination of the developmental fate of the mutated form of the V beta 6 chain in Mls-1+ mice by using retroviral vector-mediated gene transfer confirms the critical role played by the CDR1 residues in Mls-1 recognition in vivo. Collectively, the results indicate that the CDR1 of the TCR V beta 6 chain is involved in interacting with peptide/MHC as well as in Mls-1 recognition. The observation that the conserved residues in selective TCR V beta chains are imparting a significant contribution to Ag recognition suggests a molecular basis for the intrinsic bias of some V beta chains for MHC molecules.

Amino Acid Sequence↗

PubMed1994

Human primary immune response in SCID mice engrafted with human peripheral blood lymphocytes.

Severe combined immune deficient (SCID) mice were engrafted with human peripheral blood lymphocytes (Hu-PBLs) after treatment with anti-asialo GM-1 antiserum and radiation. This pretreatment facilitates high level of Hu-PBL engraftment in the SCID mice spleen. The next day, the Hu-PBL-SCID mice were immunized with either keyhole limpet hemocyanin (KLH), or carbohydrate Ag STn (AcNeu-alpha 2-alpha 6-Gal NAc-0) conjugated to KLH or protein of circumsporozoite malaria parasite (CSP), in a mixture of complete and incomplete Freund's adjuvant (1:10 v/v). The mice were bled 14 to 16 days after immunization, and the sera analyzed for STn-, KLH-, and CSP-specific human IgG and IgM Abs. The results showed that the immunized animals had a significantly higher titer of Ag-specific human IgG and IgM Abs compared to the control Hu-PBL-SCID mice. No significant Ab cross-reactions were detected between sera from KLH-, STn-, and CSP-vaccinated Hu-PBL-SCID mice. Depletion of either human CD4+ or CD8+ cells, in Hu-PBL-SCID mice, showed that CD4+ cells were essential for the primary immune response, but depletion of CD8+ cells had no influence on the titer of Ag-specific human IgG and IgM Abs.

Animals↗

PubMed1994

Expression of the NK-TR gene is required for NK-like activity in human T cells.

NK cells lyse target cells without previous immune sensitization. A small subset of T cells also exhibits NK-like activity, which is distinct from TCR-mediated, MHC-restricted, and MHC-unrestricted cytotoxicity. We recently cloned a gene, NK-TR, which is postulated to be part of the NK target-recognition/triggering complex. To determine whether the NK-TR gene product is requisite for NK-like killing, stable antisense transfectants were generated by using a human T cell clone with NK-like activity. Two distinct antisense regions of the sequence were used to generate the transfectants alpha NK-TR and alpha Cyclo. Transfectants lost the ability to lyse NK-sensitive targets but did not lose lectin-mediated cytotoxic activity. This effect was not seen with the control vector transfectant cell line. The loss of NK-like activity by the antisense transfectant alpha NK-TR correlated with the specific decrease in endogenous NK-TR mRNA and protein. These results demonstrate the requirement for the NK-TR protein for NK-like killing. Moreover, the results have important implications for examining developmental relationship between T and NK cells and the possible roles for T cells with NK-like activity in vivo.

Base Sequence↗

PubMed1994

High level functional engraftment of severe combined immunodeficient mice with human peripheral blood lymphocytes following pretreatment with radiation and anti-asialo GM1.

The severe combined immunodeficient (SCID) mouse engrafted with human peripheral blood lymphocytes (PBLs) is a potentially useful model for the study of cancer immunotherapy. For this application, rapid, consistent, and high level engraftment of SCID mice with functional human cytotoxic effector cells is necessary. To date, short term human lymphoid cell engraftment in SCID mice has generally been low and variable. Further, most of the human cells detected within the first 30 days are found in the peritoneal cavity. The purpose of the present study was to improve short term reconstitution of human PBLs in the SCID mouse. When untreated SCID mice were injected with human PBLs, the mean level of CD3+ cells in the spleens was < 5% on days 6-32 after injection, as determined by flow cytometry (FCM). Depletion of SCID mouse natural killer (NK) cells with anti-asialo GM1 only marginally improved short term reconstitution with human CD3+ cells. Preirradiation of SCID mice with 3 Gy improved reconstitution to over 16% CD3+ cells on days 12-14 following engraftment. However, the combination of pretreatment with anti-asialo GM1 plus radiation, significantly increased the mean percentage of human CD3+ cells in the spleen to 40% within 2 weeks following injection of PBLs. Human T cells positive for CD4, CD8, TcR alpha beta, and TcR gamma delta, and human NK and B cells were detected in the spleens of irradiated plus anti-asialo GM1 pretreated SCID mice. The presence of human lymphoid cells was confirmed by immunohistologic staining. The human immune cells in these mice were shown to be functional by the in vivo demonstration of an appropriate secondary immune response to the injection of tetanus toxoid and by an in vivo proliferative response to phytohemagglutinin. Human NK cells could be found in the spleens and peripheral blood of irradiated plus anti-asialo GM1 pretreated mice. These cells were also shown to be competent by their ability to lyse the human NK sensitive tumor targets K562 and MOLT-4 in 51Cr release assays. Thus, pretreatment of SCID mice with radiation plus anti-asialo GM1 significantly improves short term human PBL engraftment and provides a potentially useful model for the study of cancer immunotherapy.

Animals↗