PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Mice, SCID”

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

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

At least 37 records · Page 2Linked to original sources
PubMed2000

Distribution of parasite stages in tissues of Toxoplasma gondii infected SCID mice and human peripheral blood lymphocyte-transplanted SCID mice.

The establishment of Toxoplasma gondii infection in the tissues of SCID mice and SCID mice transplanted with human peripheral blood lymphocytes (PBL) was investigated. The presence of bradyzoites and tachyzoites was analysed in hu-PBL SCID mice using Southern blot of reverse transcriptase-polymerase chain reaction products for the expression of B1, BAG1 and SAG1 of T. gondii. BAG1 was present by week 1 in brain, lung, liver and spleen of some animals; by week 3, BAG1 was present in all animals and in all of these tissues. In contrast, SAG1 was rarely detected until week 2 (mainly in the lung and brain) and by week 3, some animals still did not have detectable SAG1 in brain, lung, liver and spleen. SAG1 expression was increased in the lungs of animals transplanted with human PBL compared to nontransplanted SCID mice. Human PBL engraftment was demonstrated, initially in uninfected mice, by the presence of human CD3+ T cells in the spleen (3.1 x 10(5) positive cells) and peritoneal cavity (3.4 x 10(5) cells) 4 weeks after transplantation. The final outcome of infection was not influenced by the presence of human PBL, with similar mortality in human PBL transplanted and nontransplanted mice. These studies provide a detailed analysis of the kinetics and distribution of both the cyst and tachyzoite stage of T. gondii. This system has been established to allow evaluation of therapies against T. gondii immunodeficient mice in the presence of human immune cells.

Animals↗
PubMed1996

Establishment and characterization of new human Burkitt's lymphoma cell lines (HBL-7 and HBL-8) that are highly metastatic in SCID mice: a metastatic SCID mouse model of human lymphoma lines.

Two newly established human Burkitt's lymphoma cell lines (HBL-7 and HBL-8) were characterized by immunophenotypic, cytogenetic and molecular studies. Both cell lines were negative for Epstein-Barr virus (EBV) genome and had chromosomal translocation: t(8;14) (q24;q32). Immunoglobulin (Ig) gene rearrangement analyses confirmed that both cell lines were derived from primary lymphoma cells. These cell lines were heterotransplanted subcutaneously into severe combined immunodeficiency (SCID) mice to investigate the metastatic capacity. The most striking feature of both cell lines was to show highly spontaneous metastasis to distant organs, particularly spleen, bone marrow and ovaries in SCID mice. To elucidate the metastatic factors involved in the process of spontaneous metastasis, cell surface adhesion molecules or extracellular matrix receptors were analyzed. However, the results did not allow a significant correlation between expression levels of those molecules or matrix receptors and spontaneous metastasis in the SCID mouse model. The HBL-7 and HBL-8 cell lines, however, may be a useful tool to elucidate the metastatic mechanisms of human lymphomas in an animal model.

Adolescent↗
PubMed1991

CD3+ T cells in severe combined immunodeficiency (SCID) mice. V. Allogeneic T cells engrafted into SCID mice do not induce graft-versus-host disease in spite of the absence of host veto and natural suppressor cell activity.

Intravenous injection of 10(6) to 10(7) non-fractionated spleen cells (SC) from C57BL/6 (B6, H-2b) mice into completely allogeneic, immunodeficient H-2d severe combined immuno deficiency (scid) mice leads to engraftment of allogeneic donor T cells. Mice analysed in the tenth week posttransfer had engrafted donor-type CD4+ and CD8+ T cells in the spleens but showed no clinical evidence of graft-versus-host disease (GVHD). Transfer of allogeneic T cells engrafted in scid recipients did not induce GVHD upon i.v. injection into secondary scid recipients and lead in most recipients to engraftment of a pure CD4+ T-cell population. Experiments were carried out to investigate the reason(s) for the lack of GVHD in recipient scid mice, i.e. the presence of allotolerance in the engrafted donor T cells. Scid spleen cells (SC) efficiently stimulated alloreactive responses of B6 T cells: scid SC stimulated H-2d-specific cytotoxic responses in a B6 anti-scid mixed lymphocyte culture in vitro, and scid SC injected i.v. into B6 mice efficiently primed splenic cytotoxic lymphocyte precursors against H-2d alloantigens. Moreover when assayed in vitro, no veto activity or natural suppressor activity was detectable in scid SC. These data demonstrate that tolerizing mechanisms currently believed to operate in vivo can not explain the fact that allogeneic T cells injected i.v. into immunodeficient scid mice become tolerized against host-type alloantigens. Our results are discussed in the light of clinical experience of allogeneic T-cell transfer in scid infants.

Animals↗
PubMed1991

CD3+ T cells in severe combined immunodeficiency (scid) mice. II. Transplantation of dm2 lymphoid cells into semi-allogeneic scid mice.

Intravenous injection of nonfractionated BALB/c-H-2dm2 (dm2) (Ld-) spleen cells into 4-week-old, semi-allogeneic (H-2d, Ld+) C.B-17 scid/scid severe combined immunodeficient (scid) mice (2 x 10(7) cells/mouse) reconstituted T lymphopoiesis in thymi and repopulated the lymphoid white pulp in spleens of these immunodeficient recipients. Transplantation of dm2 thymocytes into young scid mice (5 x 10(7) cells/mouse) established a donor-derived CD3+ T cell population in spleens of recipient scid mice, in which CD4+T cells predominated. This was demonstrated by marker analyses of thymocytes and splenocytes, and determinations of serum immunoglobulin levels in transplanted scid mice. Transfer of splenocytes from young primary scid recipients into young secondary or tertiary recipients (3 x 10(6) cells/mouse) engrafted preferentially dm2-derived CD3+CD4+CD8- T cells in spleens of scid mice despite the strong selective Ld-associated alloantigenic stimulus for CD8+ T cells. Intravenous injections of nonfractionated dm2 spleen cells (2 x 10(7) cells/mouse) or thymocytes 5 x 10(7) cells/mouse) into 10- to 12-month-old, "leaky" scid mice induced severe clinical signs of graft-vs.-host disease (GVHD) in all scid recipients. Lymphoid repopulation of spleen and thymus in old scid recipients was incomplete. This GVHD was not transferrable by injecting 3 x 10(6) spleen cells from old diseased primary scid recipients into secondary or tertiary young scid recipient mice. In these serial transfers, dm2-derived CD3+CD4+CD8- T cells were again preferentially engrafted in spleens of scid recipients. Transfer of purified CD4+ dm2 T cells into young scid mice (2 x 10(5) to 5 x 10(5) cells/mouse) engrafted this T cell subset into the spleen of semi-allogeneic scid recipients. This was revealed by histological examinations, surface marker analyses, in vitro isolation of donor-type CD3+CD4+ T cell lines from spleens of transplanted scid mice, and serial transfer experiments. These data indicated that the CD4+ T cell compartment of scid mice can be selectively repopulated by semi-allogeneic T cells. Injections of purified CD8+ dm2 T-cells into young scid mice (2 x 10(5) cells/mouse) did not establish a CD8+ T cell graft in spleens of recipients. It was necessary to inject transplanted scid mice biweekly with 10(4) units recombinant interleukin 2 to establish and/or maintain transferred dm2 CD8+ T cells in spleens of these recipients, dm2 CD8+ T cell-transplanted and interleukin 2-treated scid mice did not develop any evidence of GVHD over the 9-week observation period.

Age Factors↗
PubMed1998

Distinct in vivo engraftment and growth patterns of t(1;19)+/E2A-PBX1+ and t(9;22)+/BCR-ABL+ human leukemia cells in SCID mice.

The SCID mouse represents a valuable tool for assessing growth characteristics and drug sensitivity of human leukemic cells. We have examined differences in the engraftment patterns in SCID mice of primary human leukemic cells isolated from children (< 21 years old) with either t(1;19)+/E2A-PBX1+ or t(9;22)+/BCR-ABL+ acute lymphoblastic leukemia. Leukemic cells from 13/24 t(1;19)+/E2A-PBX1+ patients caused overt leukemia in SCID mice. Macroscopic lesions were evident in 6/13 cases, with multiple sites involved in some mice: hepatomegaly,(3) splenomegaly(4), thymic enlargement; liver tumors(1), kidney tumors(1), abdominal tumors(1). Microscopic lesions in SCID mouse organs were present in all 13 cases and involved the bone marrow, brain, heart, gut, liver, kidney, lung, ovary, pancreas, skeletal muscle, spleen, and thymus. Leukemic cells from 5/20 t(9;22)+/BCR-ABL+ patients caused overt leukemia in SCID mice. Notably, macroscopic lesions (splenomegaly; leukemic bones; hepatic tumors) were observed in only 1 case. In all 5 cases, microscopic lesions were found in the mouse bone marrow. Additional microscopic lesions were restricted to skeletal muscle, spleen, and mesentery (1 case) or thymus (1 case). These findings differ markedly from those of t(1;19)+/E2A-PBX1+ leukemic cells due to the lack of involvement of major organs such as liver, pancreas, kidney, skin, or brain. These data illustrate the biological heterogeneity of childhood ALL and suggest that the differential risks associated with t(1;19)+/E2A-PBX1+ and t(9;22)+/BCR-ABL ALL might arise from unique engraftment and proliferation capabilities of the respective leukemic cell populations.

Adolescent↗
PubMed1991

CD3+ T cells in severe combined immunodeficiency (scid) mice. IV. Graft-vs.-host resistance of H-2d scid mice to intravenous injection of allogeneic H-2b (C57BL/6) spleen cells.

Intraperitoneal injection of 2 x 10(7) nonfractionated spleen cells (SC) from C57BL/6 (B6, H-2b) mice into completely allogeneic immunodeficient H-2d scid mice induced clinical and histological signs of acute graft-vs.-host disease (GVHD), with all transplanted severe combined immunodeficiency (scid) mice dying in the 3rd week post-transfer. In contrast four out of five scid mice survived for greater than 7 weeks after intravenous (i.v.) injections of equal numbers of B6 SC. Intravenously allotransplanted scid mice analyzed in the 8th week post-transfer had engrafted donor-type CD4+ and CD8+ T cells in the spleens but showed no clinical or histological evidence of GVHD. i.v. injection of 10(7) or 10(6)O B6 SC engrafted allogeneic T cells in spleens of scid recipients; in contrast, i.v. injection of 10(5) nonfractionated B6 SC or 3 x 10(5) cell sorter-purified, naive or anti-H-2d-primed splenic CD4+ or CD8+ B6 T cells led to rejection by young scid recipient mice. B6 T cells engrafted into spleens of scid mice after i.v. injection showed proliferative anti-host alloreactivity in vitro. No cytotoxic reactivity against host-type alloantigens was found in standard 4-h 51Cr-release assays. These data demonstrate that allogeneic T cells injected i.v. into immunodeficient scid mice are partially tolerized against host-type alloantigens.

Animals↗
PubMed2002

Genetic basis of attenuation of dengue virus type 4 small plaque mutants with restricted replication in suckling mice and in SCID mice transplanted with human liver cells.

Mutations that restrict replication of dengue virus have been sought for the generation of recombinant live-attenuated dengue virus vaccines. Dengue virus type 4 (DEN4) was previously grown in Vero cells in the presence of 5-fluorouracil, and the characterization of 1248 mutagenized, Vero cell passaged clones identified 20 temperature-sensitive (ts) mutant viruses that were attenuated (att) in suckling mouse brain (J. E. Blaney, Jr., D. H. Johnson, C. Y. Firestone, C. T. Hanson, B. R. Murphy, and S. S. Whitehead, 2001, J. Virol. 75(20), 9731-9740). The present investigation has extended these studies by identifying an additional 22 DEN4 mutant viruses which have a small plaque size (sp) phenotype in Vero cells and/or the liver cell line, HuH-7. Five mutant viruses have a sp phenotype in both Vero and HuH-7 cells, three of which are also ts. Seventeen mutant viruses have a sp phenotype in only HuH-7 cells, 13 of which are also ts. Each of the sp viruses was growth restricted in the suckling mouse brain, exhibiting a wide range of reduction in replication (9- to 100,000-fold). Complete nucleotide sequence was determined for the 22 DEN4 sp mutant viruses, and nucleotide substitutions were found in the 3'-untranslated region (UTR) as well as in all coding regions except NS4A. Identical mutations have been identified in multiple virus clones, suggesting that they may be involved in the adaptation of DEN4 virus to efficient growth in Vero cells. Six of the 22 sp 5-FU mutant viruses lacked coding mutations in the structural genes, and 17 recombinant DEN4 viruses were generated which separately encoded each of the mutations observed in these six sp viruses. Analysis of the recombinant DEN4 viruses defined the genetic basis of the sp, ts, and att phenotypes observed in the six sp viruses. Mutations in NS1, NS3, and the 3'-UTR were found to confer a greater than 100-fold, 10,000-fold, and 1000-fold reduction in replication of rDEN4 virus in SCID mice transplanted with HuH-7 cells, respectively, which serves as a novel small animal model for DEN4 infection.

Animals↗
PubMed1990

T-cell receptor gene rearrangements in functional T-cell clones from severe combined immune deficient (scid) mice: reversion of the scid phenotype in individual lymphocyte progenitors.

The severe combined immune deficient (scid) mouse mutant is characterized by a general absence of functional B and T lymphocytes. This deficiency appears to result from a defect in the variable-diversity-joining (VDJ) recombinase system, which is responsible for the assembly of V, D, and J gene segments that code for immunoglobulin and T-cell receptor (TCR) V regions. Most rearranged immunoglobulin or TCR genes in transformed scid lymphocytes contain abnormal J-associated deletions and are nonfunctional. A few functional lymphocyte clones do arise, however, in some young adult scid mice and in virtually all old scid mice; this phenomenon is referred to as leakiness. Alloreactive, CD3+ T-cell clones were isolated from leaky scid mice and the status of their TCR beta and gamma loci was examined in an effort to assess the nature of the recombinase activity that gives rise to functional scid lymphocytes. The recombination junctions of six gamma and two beta alleles were sequenced, representing four alloreactive T-cell clones. All of the junctions were indistinguishable from those seen in normal cells. These results cannot be attributed to selection by antigen because other rearranged TCR genes account for the TCR molecules expressed by these T-cell clones. We conclude that reversion of the scid phenotype can occur in rare lymphocyte progenitors and may account for most functional lymphocyte clones in leaky scid mice.

Animals↗
PubMed2000

Decontamination of a Mycoplasma-infected Chlamydia pneumoniae strain by pulmonary passage in SCID mice.

We describe a procedure to eliminate contaminating Mycoplasma from Chlamydia pneumoniae (C. pneumoniae) cultures by pulmonary passage in severe combined immunodeficiency mice (SCID). Four weeks after experimental infection only C. pneumoniae could be cultured from the lungs of the infected animals while Mycoplasma could not be detected any longer, as shown by PCR, culture and transmission electron microscopy (TEM).

Animals↗
PubMed1998

Treatment of non-obese diabetic (NOD)/Severe-combined immunodeficient mice (SCID) with flt3 ligand and interleukin-7 impairs the B-lineage commitment of repopulating cells after transplantation of human hematopoietic cells.

Until recently, the identification of cellular factors that govern the developmental program of human stem cells has been difficult due to the absence of repopulation assays that detect human stem cells. The transplantation of human bone marrow (BM) or cord blood (CB) into non-obese diabetic (NOD)/severe-combined immunodeficient (SCID) mice has enabled identification of primitive human cells capable of multilineage repopulation of NOD/SCID mice (termed the SCID-repopulating cell [SRC]). Here, we examined the effect of long-term in vivo treatment with various combinations of human cytokines on the developmental program of SRC. Detailed flow cytometric analysis of engrafted mice indicated that the vast majority of the human graft of untreated mice was comprised of B lymphocytes at various stages of development as well as myeloid and primitive cells; T cells were not reproducibly detected. Many studies, including murine in vitro and in vivo data and human in vitro experiments, have suggested that flt3 ligand (FL) and/or Interleukin-7 (IL-7) promotes T- and B-cell development. Unexpectedly, we found that treatment of engrafted mice with the FL/IL-7 combination did not induce human T- or B-cell development, but instead markedly reduced B-cell development with a concomitant shift in the lineage distribution towards the myeloid lineage. Effects on lineage distribution were similar in engrafted mice transplanted with highly purified cells indicating that the action of the cytokines was not via cotransplanted mature cells from CB or BM cells. These data show that the lineage development of the human graft in NOD/SCID mice can be modulated by administration of human cytokines providing a valuable tool to evaluate the in vivo action of human cytokines on human repopulating cells.

Animals↗
PubMed1992

Comparative studies between nude and scid mice on the growth and metastatic behavior of xenografted human tumors.

The growth and metastatic behavior of three human tumor cell lines and a human colon carcinoma previously passaged in vivo were compared between nude mice and scid mice after xenotransplantation. The three human tumor lines included a bladder carcinoma (T24B), a melanoma (RPMI 7931) and a lacZ gene-transduced breast cancer (MDA-MB-435 BAG). The lacZ gene codes for beta-galactosidase, which can be stained blue with chromogenic substrate X-gal, thus allowing the highly sensitive detection and quantitative examination of human cancer metastasis in host mice. Adult (7-14 weeks) NMRI nude and C.B-17 SCID mice were inoculated with 0.5-5 x 10(6) tumor cells s.c. Comparable take rate, latent period and growth rate of implanted tumors were observed in nude and scid mice for each of the cell lines tested. At the time of autopsy, which varied from 6 to 11 weeks after inoculation, a significantly higher incidence of spontaneous lung metastasis was discovered in scid mice (96%) than in age-matched nude mice (27%, total P less than 0.001). In vitro assays for NK cell-mediated cytotoxicity revealed no significant differences between the two strains of mice. Our results suggest that nude and scid mice are equally suitable for propagating human tumors. However, the metastatic capacity of human tumor cells appears to be better expressed in scid mice. Scid mice may therefore provide an advantageous model for the study of human tumor metastasis.

Animals↗
PubMed1988

Transcription of unrearranged antigen receptor genes in scid mice.

The scid mouse mutant is severely deficient in lymphocytes; cells of the B or T lymphocyte lineage cannot be detected by either serological or functional assays. However, as shown here, germ-line transcripts of B cell immunoglobulin (Ig) constant and variable region genes and of T cell receptor (TCR) genes are detectable in lymphopoietic tissues of scid mice, as well as B and T lineage-specific lambda 5 and T3 delta transcripts. We conclude that B and T lineage-committed cells do arise in scid mice and that their Ig and TCR genes are accessible to enzymes involved in their recombination. This suggests that scid impairs lymphopoiesis at the stage at which antigen receptor genes normally undergo rearrangement.

Animals↗
PubMed1991

CD3+ T cells in severe combined immune deficiency (scid) mice. I. Transferred purified CD4+ T cells, but not CD8+ T cells are engrafted in the spleen of congenic scid mice.

Young (less than 3 months of age) and old (greater than 1 year of age) C.B-17 scid/scid mice were tested for the presence of immunoglobulin in serum and CD3+ T cells in spleen and peritoneal cavity. In all old severe combined immune deficiency (scid) mice tested we found detectable, but very variable levels of serum immunoglobulin as well as splenic and peritoneal CD3+ T cells comprising 3% to 10% of the nonfractionated cell populations of these organs (n = 10). In contrast, none of the analyzed young scid mice showed any evidence of peripheral lymphocytes. Low numbers (2 x 10(5) to 5 x 10(5) cells/mouse) of highly purified CD4+ cells from congenic C.B-17 or BALB/c donor mice were injected intravenously into young scid recipient mice. A CD4+ T cell population was clearly engrafted when transplanted scid mice were analyzed 8 to 13 weeks after T cell transfer: (a) a CD3+CD4+CD8- T cell population was detectable in the spleens of all recipient scid mice by flow microfluorometry analyses; (b) CD3+CD4+CD8 T cell lines could be grown out of these spleens in vitro; (c) the histological examination revealed evidence of lymphoid cell repopulation in the spleens of all transplanted scid mice and (d) transplanted CD4+ T cell populations could be serially transferred into secondary and tertiary recipient scid mice. These data indicate that scid mice can be constructed in which only the CD4+ T cell compartment is selectively reconstituted. In contrast to the successful engraftment of CD4+ T cell, highly purified congenic CD8+ T cells could not be engrafted into the spleen of scid mice.

Aging↗
PubMed1992

CD4+CD8- thymocytes from neonatal mice induce IgM production in SCID mice.

Defective recombination of both the TCR and Ig genes results in the absence of mature lymphocytes in mice with the scid mutation. We have shown previously that the transfer of neonatal, but not adult, thymocytes results in high levels of Ig production in 100% of C.B-17-scid (SCID) mice, in contrast to the 10 to 25% of SCID mice spontaneously producing low levels of oligoclonal Ig. In this report we demonstrate that neonatal CD4+8- thymocytes were able to induce this response; the CD4+8+ and CD4-8+ subpopulations were totally inactive and CD4-8- T cells had only limited activity several weeks after transfer. The stimulation of IgM production in SCID mice was detectable by 1 wk posttransfer of CD4+8- thymocytes or splenic T cells, and could be achieved with as few as 300 cells. The ability of neonatal CD4+8- thymocytes to induce Ig diminished gradually to insignificant levels at 3 wk postbirth; this loss of function was not associated with differential survival of neonatal T cells. Neonatal CD4+8- thymocytes from C.B-17 and other H-2d strains rescued Ig production, whereas cells from H-2b, H-2a, and H-2k strains were much less effective. These results suggest that a CD4+8- subpopulation found in both neonatal thymus and peripheral lymphoid tissues is able to induce the expansion or differentiation of the small numbers of functional B lymphocytes in SCID mice, and that the inducing T cell disappears shortly after birth, perhaps during the acquisition of self-tolerance.

Age Factors↗
PubMed1994

Effect of removing human Graves' thyroid xenografts after eight weeks in nude mice and rexenografting them into SCID mice.

Human thyroid xenografts from four patients with Graves' disease (GD) and two normal persons were initially xenografted into nude mice. Eight weeks after xenografting, the thyroid tissue appeared normal; indeed, thyroid infiltrating lymphocytes in the GD xenograft could no longer be identified when analyzed histologically. Thus, human immunoglobulin G (IgG), thyroperoxidase (TPO)-antibodies (Abs), thyroglobulin (Tg)-Abs, thyroid-stimulating antibodies (TSAb), and thyrocyte histocompatibility leucocyte antigen (HLA)-DR expression were undetectable. These same tissues were retrieved from the nude mouse and rexenografted into severe combined immunodeficient (SCID) mice (with no prior xenograft); autologous peripheral blood mononuclear cells (PBMC) or CD8-depleted PBMC (non-CD8 cells) were simultaneously injected into some of these SCID mice. Engraftment of a GD thyroid rexenograft (TH) alone did not cause IgG, TSAb, TPO-Ab, or Tg-Ab production, thyrocyte HLA-DR expression, or lymphocytic infiltration in thyroid grafts. Engraftment of GD PBMC or non-CD8 cells alone (i.e. without a thyroid xenograft) caused human IgG to rise, but only minimal titers of thyroid antibodies appeared. When TSAb, TPO-Ab, and Tg-Ab were quantified, GD TH plus PBMC-engrafted SCID mice showed significantly higher production of each antibody than that of GD PBMC alone, and this phenomenon was further enhanced by the removal of CD8+ cells. GD thyrocytes showed marked HLA-DR expression at human surgery; however, after 8 weeks' sojourn in nude mice, DR expression disappeared. After a further 8 weeks following rexenografting into SCID mice, TH plus PBMC resulted in a reappearance of DR expression only in GD but not in grafts from normal persons, and this was enhanced by the depletion of CD8 cells. These results were also in parallel with histological findings inasmuch as the normal tissue remained normal with no thyroid antibodies appearing with PBMC or CD8-depleted cells. In experiments from two GD patients, autologous skeletal muscle as well as thyroid tissue were xenografted into nude mice. Eight weeks after xenografting, these were rexenografted into SCID mice that contained prior autologous primary GD thyroid xenografts. Histological findings showed new lymphocytic infiltration in rexenografted thyroid tissues in the SCID mice but not in autologous skeletal muscle. This signifies that the immune assault in GD is specifically targeted to the thyroid tissue.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1997

Hantavirus infection in SCID mice.

Severe combined immunodeficiency (SCID) mice were inoculated with Hantaan virus strain 76-118 (HTN) or Seoul virus strain SR-11 (SR) of hantaviruses. Susceptibility of SCID mice was compared with those of immunocompetent adult mice, newborn mice and nude mice. SCID mice inoculated with HTN or SR died 32 to 35 days after infection. Unlike newborn mice which also died of hantavirus infection, SCID mice survived longer than newborn mice and showed typical wasting symptoms rather than nervous symptoms. Immunohistochemical staining and virus isolation indicated that both HTN and SR inoculated SCID and SR inoculated nude mice showed systemic infection, but nude mice inoculated with SR survived for longer than 8 weeks after inoculation. Passive transfer of spleen cells from immunocompetent BALB/c mice conferred protection on SCID mice within 2 weeks of HTN infection. Immune mediated pathologic mechanism was examined by transferring the spleen cells to SCID mice inoculated with HTN virus 3 weeks before the cell transfer. The recipient SCID mice showed an increase of serum BUN level coinciding with the appearance of serum antibody to HTN virus, suggesting the immune mediated pathogenicity.

Adoptive Transfer↗
PubMed2001

[Establishment and characterization of three transplantable tumors of nasopharyngeal carcinoma in Scid mice].

BACKGROUND: To establish several transplantable tumors of nasopharyngeal carcinoma (NPC) in order to provide suitable models for study of EBV specific immunity and its application in treatment of NPC. METHODS: Balb/C nude mice and scid mice were used as transplantation host. Tumor tissues were obtained with forceps from nasopharyngeal tumors of twenty six untreated NPC patients and transplanted subcutaneously in axilla or back of mice with puncture trocar. Characteristics of the established transplantable tumors including the transplanting efficiency, growth rate, gross appearance morphology under optic microscope and electron microscope and karyotypes chromosome were investigated. Detection of LMP-1 as well as LMP-2 were performed for the transplantable tumors and cell lines with immunohistochemical methods. RESULTS: Three transplantable tumors were successfully established from 26 specimens of human nasopharyngeal carcinoma and mamed as CSNET-1, CSNET-2 and CSNET-3. The CSNET-1 was primarily generated in nude mice and then transplanted to scid mice after 3 passages. To date the CSNET-1, CSNET-2, CSNET-3 have been passed to 11th generation (23 months), 14th generation (17 months) and 9th generation (16 months), respectively. The overall success rates of transplantation were 91% (39/43), 97% (29/30) and 94% (34/36); The median time of latent growth were 23, 38 and 20 days;and longest persistence of tumor in vivo were 93, 38 and 44 days, respectively, for the above tumors. The karyotypes of all transplantable tumors displayed as typical human origin with hyperdiploid chromosomal and multiple structure aberration. Histologically, the tumors possess the characteristics of poor differentiated squamous carcinoma under either microscope or electron microscope. Some particles minimizing mature EBV were found in CSNET-1 under electron microscope. Either LMP-1 or LMP-2 were detectable in CSNET-1, CSNET-2, and CSNET-3 by immunohistochemical test. CONCLUSIONS: The transplantable tumors CSNET-1, CSNET-2 and CSNET-3 are of human origin and able to pass steadily in scid mice. They possess the characteristics of poorly differentiated squamous carcinoma similar to their prime tumors in human and express EBV LMP-1 and LMP-2. These tumors seemed to be suitable models in the study of immunotherapy for NPC.

Animals↗