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Results for “SCID mouse”

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PubMed1996

Selective homing of human leukemic B-cell precursors to specific lymphohematopoietic microenvironments in SCID mice: a role for the beta 1 integrin family surface adhesion molecules VLA-4 and VLA-5.

We used a SCID mouse xenograft model to study the in vivo growth patterns of primary leukemic cells from six patients with newly diagnosed B-cell precursor (BCP) acute lymphoblastic leukemia (ALL), including two patients with t(1;19) ALL, two patients with t(4;11) ALL, and two patients with t(9;22) ALL. Leukemic cells from these six patients caused overt leukemia in SCID mice with extensive multiple organ involvement. Leukemic BCP from SCID mice xenografted with leukemic cells from two t(9;22) ALL patients expressed very high levels of both VLA-4 and VLA-5 regardless of the tissue of origin. By comparison, in SCID mice xenografted with leukemic cells from the two patients with t(1;19) ALL and two patients with t(4;11) ALL, leukemic BCP from the bone marrow samples expressed high levels of VLA-4 as well as VLA-5, whereas the vast majority of leukemic BCP in the liver or spleen samples expressed neither of these adhesion molecules at significant levels. These results suggest that the expression of VLA-4 and VLA-5 on t(1;19) or t(4;11) leukemia cells likely determines their binding capacity to bone marrow stroma and may affect their migration to extramedullary tissues. Our findings are in accord with and extend previous studies which demonstrated that extracellular matrix and integrins influence development, compartmentalization, and migration of BCP during B-cell ontogeny. The described SCID mouse model system provides a unique opportunity to study the adhesion receptors which regulate the selective homing of human leukemic BCP to specific SCID mouse organs.

Animals↗

PubMed1996

Transplantation of a human ovarian cystadenocarcinoma into severe combined immunodeficient (SCID) mice--formation of metastases without significant alteration of the tumour cell phenotype.

Human ovarian papillary cystadenocarcinoma cells were injected intraperitoneally into severe combined immunodeficient (SCID) mice. After intraperitoneal application the cells, designated SoTü, grew well in vivo, lodged on to the peritoneum, formed local metastatic deposits, led to the development of ascites in the mice and formed distant metastases in the lungs. If lodged in the ovary, the morphology of the SoTü tumour remarkably resembled that of the primary tumour in the patient. In contrast, several attempts failed to maintain the SoTü cells in vitro. If SCID mouse ascites derived SoTü were transplanted subcutaneously in SCID mice, they formed cystic tumours which also metastasized into the lungs. Immunophenotypical analysis of cell adhesion molecule expression, cell proliferation markers, various oncoproteins, keratin, vimentin, and lectin binding site expression all showed striking similarity between the primary tumour and the SCID mouse explants. In particular, expression of binding sites for the lectin Helix pomatia agglutinin (HPA), which has been shown to be an index of metastatic potential in several human carcinomas, was found on the primary tumour as well as on tumour cells grown in SCID mice, indicating that HPA might be a prognostic indicator in ovarian carcinoma as well. Our results demonstrate that the human/SCID mouse system can mimic growth and distant metastasis formation of human ovarian carcinoma. Although the formation of distant metastases is a relatively rare event in patients, this model system might help to elucidate mechanisms of metastasis formation in ovarian cancer.

Animals↗

PubMed2001

Serum-free coculture system for ex vivo expansion of human cord blood primitive progenitors and SCID mouse-reconstituting cells using human bone marrow primary stromal cells.

OBJECTIVE: In an attempt to maintain and expand human stem cells, many investigators have used xenogeneic, especially murine, stromal cells and fetal calf serum. Because of the possible transmission of infectious diseases, however, the safety of the delivery of grafts expanded in culture using xenogeneic cells and serum has been debated. Using primary human marrow stromal cells, we established a novel serum-free culture system to expand human primitive progenitors and transplantable stem cells. MATERIALS AND METHODS: Cord blood CD34(+) cells were cultured on a monolayer of human primary marrow stromal cells in the presence of thrombopoietin (TPO), flt3/flk2 ligand (FL), and/or stem cell factor (SCF) under serum-free conditions. After 2 or 4 weeks of culture, cells were examined for clonogenic progenitors and severe combined immunodeficient disorder (SCID) mouse-reconstituting cells (SRC). RESULTS: In the presence of TPO, FL, and SCF, marrow stromal cells supported more than a 100- and 1,000-fold expansion of CD34(+) cells and colony-forming units in culture after 2 and 4 weeks of incubation, respectively. In addition, cobblestone area-forming cells were expanded more than 18- and 60-fold after 2 and 4 weeks of culture, respectively. Furthermore, SRC assay demonstrated augmented engraftment by cultured cells. CONCLUSION: This ex vivo expansion system should prove valuable in clinical settings in which stromal cells are available from recipients or stem cell donors.

Acute Disease↗

PubMed1997

Physiologic human T-cell responses to OKT3 in the human peripheral blood lymphocyte-severe combined immunodeficiency mouse model.

BACKGROUND: Our goal was to study physiologic responses of human T lymphocytes to OKT3 in the human peripheral blood lymphocyte-severe combined immunodeficiency (hu-PBL-SCID) mouse model. METHODS: SCID mice were pretreated with anti-asialo-GM1 (alpha-ASGM1) and radiation, then engrafted with human peripheral blood lymphocytes (PBLs). Seven to 14 days after engraftment, when most human T cells in the spleen of these mice are CD3+/CD4+ and CD3+/CD8+, mice were treated with OKT3 or control antibody. Mice were killed for histopathologic examination, for flow cytometric assessment of the engrafted human lymphocytes, and for analysis of human tumor necrosis factor-alpha serum levels. RESULTS: Intravenous injection of 5 microg of OKT3 resulted in early antigenic modulation of engrafted human T lymphocytes, with the emergence of CD3-/CD4+ and CD3-/CD8+ cells in the spleen of hu-PBL-SCID mice. There was an increase in the serum concentration of human tumor necrosis factor-alpha within 4 hr after OKT3 injection, suggesting early T-cell activation. Antigenic modulation and activation of the human lymphocytes in the spleen was followed by their depletion within 24 hr. This human T-cell response to OKT3 in hu-PBL-SCID mice is analogous to the response in humans treated with OKT3 and in BALB/c mice injected with an anti-murine CD3 monoclonal antibody. Graft-versus-host disease in the mice was abrogated by OKT3 treatment, and OKT3-treated mice lived longer than controls. Histopathologic studies showed clearance of lymphocytic infiltration in the liver and lungs of OKT3-treated mice. CONCLUSIONS: These findings provide further evidence of functional human immune T cells in the hu-PBL-SCID mouse. This model may have useful applications in the study of transplantation immunology.

Animals↗

PubMed2002

RNA-based anti-HIV-1 gene therapeutic constructs in SCID-hu mouse model.

Effective suppression of HIV-1 replication requires inhibition of critical viral target molecules. Tat and Rev are indispensable regulatory factors for HIV-1 replication, whereas Env mediates virus entry by direct interaction with surface receptor CD4 and coreceptor CCR5 or CXCR4. Anti-HIV-1 tat-rev and env ribozymes and Rev aptamers were previously demonstrated to provide relatively long-term protection against HIV-1 infection in vitro. However, further improvements in these constructs for clinical application in a stem-cell-based gene therapy setting requires in vivo characterization. Toward this end, we introduced these constructs into CD34(+) hematopoietic progenitor cells by retrovirus-mediated gene transduction. Ribozyme- and aptamer-transduced CD34(+) cells differentiated normally into multiple lineages of erythroid and myeloid progenies in a colony-forming unit assay. Macrophages that differentiated from the transduced CD34(+) cells expressed anti-tat-rev and -env ribozymes and Rev aptamers and displayed their normal characteristic surface markers CD14, CD4, and CCR5. Using the SCID-hu mouse in vivo human thymopoiesis model, we demonstrated that ribozyme- and aptamer-transduced CD34(+) cells retained their normal capacity to reconstitute human fetal thymus and liver tissue (thy/liv) grafts. Reconstitution by ribozyme- and aptamer-transduced CD34(+) cells reached levels of up to 87% based on HLA surface marker staining. Differentiated thymocytes derived from reconstituted grafts expressed anti-tat-rev and -env ribozymes and Rev aptamers and showed significant resistance to HIV-1 infection upon challenge. Analysis of reconstituted thymocytes by hybridization revealed an average of 0.4 to 2 copies of vector sequences per cell. Southern analysis of proviral integration junctions in progeny thymocytes demonstrated that the human thy/liv grafts were reconstituted by a few primitive hematopoietic stem cells. These results highlight the utility of RNA-based anti-HIV-1 gene therapeutic approaches and their preclinical testing in a surrogate animal model harboring human tissue.

Animals↗

PubMed1995

Conditions for engraftment of human acute myeloid leukemia (AML) in SCID mice.

Transplantation of human AML into severe combined immunodeficient (SCID) mice provides a useful experimental model but graft failures have been reported. We investigated the influence of a number of factors on the outgrowth of AML in the SCID mouse bone marrow (BM). The transplantation route and total body irradiation (TBI) were examined using the cell line HL-60 as a model for AML. The role of graft size and recombinant human IL-3 (IL-3) were investigated with patient samples of AML cells. Intravenous transplantation was demonstrated to be superior to intraperitoneal transplantation. Pretransplant conditioning resulted in a dose-dependent increase of AML growth in the SCID mouse. Cell dose titrations ranging from 3 x 10(7) - 3.6 x 10(5) AML cells i.v. per mouse revealed a minimum of 1.1 x 10(6) required for reproducible engraftment. Earlier and more extensive infiltration by human AML cells was seen following injection of greater cell numbers. IL-3 given post-transplantation SCID mouse recipients, promoted AML growth in three cases, whereas a fourth AML cell specimen also grew without support of IL-3. In vitro growth factor responsiveness of AML cells to IL-3 did not predict IL-3 dependence of AML growth in vivo.

Acute Disease↗

PubMed2006

Therapeutic intervention of experimental breast cancer bone metastasis by indole-3-carbinol in SCID-human mouse model.

Several lines of experimental evidence have suggested that chemokine receptor CXCR4, a metastasis-promoting molecule, may play important roles in breast cancer bone metastasis. There is emerging evidence linking CXCR4 to matrix metalloproteinases (MMP) as well as their regulator nuclear factor-kappaB (NF-kappaB), a key transcription factor, which is known to activate metastasis-promoting molecules for many types of malignancies, including breast cancer. A recent study also showed that promoter region of CXCR4 has several NF-kappaB-binding sites, suggesting that there may be a cross-talk between CXCR4 and NF-kappaB. We have shown previously that indole-3-carbinol (I3C), a natural compound present in vegetables of the genus Brassica, can inhibit NF-kappaB in breast cancer cells. However, there are no reports in the literature showing any effect of I3C on CXCR4 expression in vitro and in vivo. We therefore examined whether I3C could inhibit bone metastasis of breast cancer by inhibiting CXCR4 and MMP-9 expression mediated via the inhibition of the NF-kappaB signaling pathway. Here, we have modified the severe combined immunodeficient (SCID)-human mouse model of experimental bone metastasis for use with the MDA-MB-231 breast cancer cell line. In this animal model, we found that I3C significantly inhibited MDA-MB-231 bone tumor growth, and our results were correlated with the down-regulation of NF-kappaB. Moreover, we found that I3C significantly inhibited the expression of multiple genes involved in the control of metastasis and invasion in vitro and in vivo, especially the expression of CXCR4 and MMP-9 along with pro-MMP-9, with concomitant decrease in Bcl-2 and increase in the proapoptotic protein Bax. From these results, we conclude that the CXCR4/NF-kappaB pathway is critical during I3C-induced inhibition of experimental breast cancer bone metastasis. These results also suggest that I3C could be a promising agent for the prevention and/or treatment of breast cancer bone metastasis in the future.

Animals↗

PubMed2005

Reovirus salvage of squamous cell cancer-contaminated wounds.

PURPOSE: To assess the susceptibility of human squamous cell carcinoma to reovirus infection in vitro and in vivo using a murine model of cancer-contaminated wounds. METHODS: The University of Michigan squamous carcinoma 22B cell line was cultured and inoculated with reovirus in vitro. The effect of the reovirus was assessed with microscopy and a standard 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H tetrazolium bromide (MTT) assay. We used the previously established cancer-contaminated wound SCID mouse model to test saline and reovirus irrigation in vivo. Fifty-five mice were used; 15 were controls, 20 had immediate irrigation, and 20 had delayed irrigation. Surgical sites were assessed for palpable tumour biweekly. RESULTS: The microscopy and MTT assay both showed evidence of reovirus-mediated squamous cancer cell lysis. The control mice grew palpable tumours in 80% of the wounds. Immediate irrigation with saline delayed the onset of palpable tumour and demonstrated a persistent reduction in the rate of development of palpable tumours (p = .004 compared with controls). This effect disappeared when the saline irrigation was delayed, resulting in a tumour development rate that was not significantly different from that of the control. Wounds that were irrigated with reovirus, both immediately and delayed, did not produce palpable tumour (p < .0005 when compared with controls). CONCLUSIONS: (1) The University of Michigan squamous cell carcinoma 22B cell line is susceptible to reovirus in vitro. (2) Immediate irrigation with saline resulted in a significant delay in clinically evident tumour growth and a reduction in the rate of tumour development in the SCID mouse model. (3) The reovirus irrigation resulted in a significant reduction of tumour development in both the immediate and delayed groups in the SCID mouse model. (4) The efficacy of the reovirus irrigation in the delayed group suggests that the major mechanism of action is through a selective and specific targeting of implanted cancer cells.

Animals↗

PubMed1992

High human IgG levels in severe combined immunodeficient mouse reconstituted with human splenic tissues from patients with gastric cancer.

We implanted normal peripheral blood lymphocytes (PBL) from healthy donors and splenic tissues from patients with gastric cancers into the severe combined immunodeficient (SCID) mouse, demonstrating that SCID mouse with splenic tissue can produce a high level of human immunoglobulin G (IgG). The normal PBLs at 10(7) and 10(8)/mouse were implanted intraperitoneally, and three splenic tissues with a size of 3 x 3 x 3 mm from gastric cancer patients were inoculated subcutaneously into the bilateral backs of the mice. At 2, 4, 6 and 8 weeks after inoculation, mice were killed, and the human IgG was assessed by an ELISA method. SCID mice with splenic tissue revealed high human IgG levels from 2 weeks after inoculation and approximately 2 mg of IgG per ml was observed at 8 weeks post-implantation, while the IgG levels in mice treated with PBLs were limited. Since the half life of the extrinsic human IgG was 10.2 days, the high level of human IgG in the SCID mice was supposed to be produced by human plasma cells in the splenic tissue from gastric cancer patients. This model was thought to be adequate for evaluating human immunological functions in vivo.

Animals↗

PubMed1993

Efficacy of anti-CD5 F(ab')2 and Fab' immunoconjugates in human peripheral blood lymphocyte-reconstituted severe combined immunodeficient mice.

A human peripheral blood lymphocyte-reconstituted severe combined immunodeficient (hu-PBL-SCID) mouse model was used to compare in vivo efficacy of immunoconjugates directed against the CD5 antigen present on human T-cells. Four anti-CD5 immunoconjugates were tested, composed of chimeric human-mouse (cH65) F(ab')2 or Fab' fragments chemically linked to recombinant gelonin (rGEL) or the 30,000 M(r) glycoform of ricin A chain (RTA30). Immunoconjugate treatment was initiated approximately 3 weeks after PBL transplantation and consisted of five consecutive daily bolus i.v. injections. Efficacy was subsequently assessed by quantitation of human T-cells in spleens, blood and peritoneal lavage fluid using 3-color flow cytometry. cH65 F(ab')2- and cH65 Fab'-rGEL conjugates were essentially equally effective at depleting human T-cells from SCID mouse tissues, suggesting that bivalent binding is not required for efficacy when rGEL is the cytotoxic moiety. Treatment with unconjugated F(ab')2, unconjugated Fab' or a Fab-rGEL immunoconjugate of irrelevant binding specificity did not result in a significant depletion of T-cells, demonstrating that the cytotoxic moiety and a relevant human T-cell binding moiety are both required for efficacy. In contrast to the results observed with the rGEL conjugates, cH65 Fab'-RTA30 was not as effective as cH65 F(ab')2-RTA30 in depleting human T-cells from SCID mouse tissues. This paralleled in vitro findings in a human PBMC cytotoxicity assay, which demonstrated that cH65 Fab'-RTA30 was 17-fold less potent than cH65 F(ab')2-RTA30 and approximately 50-fold less potent than the rGEL conjugates.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

SCID mice as models for parasitic infections.

Mice with severe combined immunodeficiency (SCID mice) have become a favored model system for the study of many parasitic diseases. In this review, Samuel Stanley Jr and Herbert Virgin IV provide a brief overview of the biology of the SCID mouse, and review some examples of how the SCID mouse model has been applied to the study of the immunology of a number of different parasitic diseases.

Journal Article↗

PubMed1995

Tissue factor promotes melanoma metastasis by a pathway independent of blood coagulation.

Several studies have established a link between blood coagulation and cancer, and more specifically between tissue factor (TF), a transmembrane protein involved in initiating blood coagulation, and tumor metastasis. In the study reported here, a murine model of human melanoma metastasis was used for two experiments. (i) The first experiment was designed to test the effect of varying the level of TF expression in human melanoma cells on their metastatic potential. Two matched sets of cloned human melanoma lines, one expressing a high level and the other a low level of the normal human TF molecule, were generated by retroviral-mediated transfections of a nonmetastatic parental line. The metastatic potential of the two sets of transfected lines was compared by injecting the tumor cells into the tail vein of severe combined immunodeficiency (SCID) mice and later examining the lungs and other tissues for tumor development. Metastatic tumors were detected in 86% of the mice injected with the high-TF lines and in 5% of the mice injected with the low-TF lines, indicating that a high TF level promotes metastasis of human melanoma in the SCID mouse model. This TF effect on metastasis occurs with i.v.-injected melanoma cells but does not occur with primary tumors formed from s.c.-injected melanoma cells, suggesting that TF acts at a late stage of metastasis, after tumor cells have escaped from the primary site and entered the blood. (ii) The second experiment was designed to analyze the mechanism by which TF promotes melanoma metastasis. The procedure involved testing the effect on metastasis of mutations in either the extracellular or cytoplasmic domains of the transmembrane TF molecule. The extracellular mutations introduced two amino acid substitutions that inhibited initiation by TF of the blood-coagulation cascade; the cytoplasmic mutation deleted most of the cytoplasmic domain without impairing the coagulation function of TF. Several human melanoma lines expressing high levels of either of the two mutant TF molecules were generated by retroviral-mediated transfection of the corresponding TF cDNA into the nonmetastatic parental melanoma line, and the metastatic potential of each transfected line was tested in the SCID mouse model. Metastases occurred in most mice injected with the melanoma lines expressing the extracellular TF mutant but were not detected in most mice injected with the melanoma lines expressing the cytoplasmic TF mutant. Results with the extracellular TF mutant indicate that the metastatic effect of TF in the SCID mouse model does not involve products of the coagulation cascade. Results with the cytoplasmic TF mutant indicate that the cytoplasmic domain of TF is important for the metastatic effect, suggesting that the TF could transduce a melanoma cell signal that promotes metastasis.

Animals↗

PubMed2004

Targeting cathepsin L (CL) by specific ribozymes decreases CL protein synthesis and cartilage destruction in rheumatoid arthritis.

The present study was undertaken to examine whether ribozymes cleaving specifically cathepsin L (CL) mRNA are able to decrease the synthesis of CL protease in rheumatoid arthritis synovial fibroblasts (RA-SF) and thereby reduce the invasiveness into cartilage both in vitro and in the SCID mouse coimplantation model of RA. Two different ribozymes that cleave CL mRNA specifically at positions 533 (RzCL533) and 790 (RzCL790) were generated. Using retroviral gene transfer, RA-SF were transduced with the ribozyme constructs or the empty vector. To examine the effect of the ribozymes on the mRNA level, quantitative analysis for CL mRNA was performed using real-time PCR. For evaluation on the protein level, ELISA using specific anti-CL antibodies was performed. In addition, transduced RA-SF were examined in vitro in a three-dimensional destruction assay evaluating their ability to degrade extracellular matrix produced by human chondrocytes. Matrix destruction was monitored by the release of soluble glycosaminoglycans (sGAG). Using the in vivo SCID mouse coimplantation model of RA, RzCL533-transduced RA-SF and control cells were coimplanted with human cartilage for 60 days. After being killed, invasion of RA-SF into the cartilage was evaluated by using a semiquantitative score. Transduction of RA-SF with RzCL533 and RzCL790 ribozymes decreased significantly the expression of CL mRNA to 44% (range 25-62%) and 20% (range 1-43%), respectively, when compared to mock-transduced cells. The protein concentration of CL in the cell culture supernatants of transduced RA-SF was decreased from 16.0 ng/ml in the mock constructs to 4.1 and 8.2 ng/ml (mean), respectively. Using the in vitro cartilage destruction assay, the release of sGAG decreased to 46 and 60%, respectively, after 14 days when compared to mock-transduced cells. In the SCID mouse coimplantation model of RA, RzCL533-transduced RA-SF revealed a significant lower cartilage invasion when compared to mock and untransduced cells. Using retroviral gene transfer, ribozymes cleaving CL mRNA inhibit specifically the synthesis of this matrix-degrading enzyme and reduce cartilage destruction in in vitro and in vivo models. Our study therefore suggests that ribozymes targeting CL could be a novel and efficient tool to inhibit joint destruction in RA.

Animals↗

PubMed1993

Gamma interferon functions in resistance to Cryptosporidium parvum infection in severe combined immunodeficient mice.

Severe combined immunodeficient (SCID) adult mice are relatively resistant to Cryptosporidium parvum infection, even though they are deficient in both T- and B-cell function. The requirement for gamma interferon (IFN-gamma) in this resistance was examined by treatment of these mice with monoclonal antibody to IFN-gamma. SCID mice injected intraperitoneally with monoclonal anti-IFN-gamma 4 h before and three times weekly after challenge with C. parvum had heavy intestinal infections 3 weeks postchallenge. SCID mice similarly injected with irrelevant antibody were not infected. Furthermore, SCID mice receiving a single injection of anti-IFN-gamma either 2 h before or 18 h after challenge were also susceptible to infection. Although IFN-gamma was not detected in SCID mouse intestinal samples, it was found in the supernatant of SCID mouse splenocyte cultures after stimulation with C. parvum antigens. On the other hand, SCID mice receiving multiple injections of antibodies against tumor necrosis factor remained resistant to infection. These data indicate that the resistance of SCID mice to C. parvum infection is IFN-gamma dependent, whereas tumor necrosis factor appears not to play a significant role.

Animals↗

PubMed2001

Shigella infection in a SCID mouse-human intestinal xenograft model: role for neutrophils in containing bacterial dissemination in human intestine.

Shigellae infect human intestine and cause intense inflammation and destruction of colonic and rectal mucosa. To model the interactions of shigella with human intestine in vivo, we have studied shigella infection in human intestinal xenografts in severe combined immunodeficient mice (SCID-HU-INT mice). Inoculation of shigella into human intestinal xenografts caused severe inflammation and mucosal damage, which was apparent as soon as 4 h following infection. Shigella infection was associated with human intestinal production of interleukin-1B (IL-1B) and IL-8 and a marked neutrophil influx into the graft. Depletion of neutrophils from SCID-HU-INT mice reduced inflammation in the human intestinal xenograft in response to shigella infection but failed to significantly alter tissue damage. However, the number of intracellular bacteria was more than 20-fold higher in the human intestinal xenografts from neutrophil-depleted SCID-HU-INT mice. Infection of human intestinal xenografts with an attenuated vaccine strain of shigella (CVD1203) induced lower levels of IL-1B and IL-8 than wild-type shigella and caused only moderate damage to the intestinal permeability barrier. Our studies establish the SCID-HU-INT mouse as a viable model for studying the interactions between shigella and human intestine and indicate that neutrophils are important for controlling the invasion of human intestine by shigella.

Animals↗

PubMed1999

Role of CD8+ and WC-1+ gamma/delta T cells in resistance to Mycobacterium bovis infection in the SCID-bo mouse.

The role of various effector T cell populations in the bovine immune response to Mycobacterium bovis infection is poorly understood. This is largely due to the difficulties associated with performing in vivo challenge studies in the natural host species. In this report, we utilized a fetal bovine-severe combined immunodeficient (SCID-bo) xenochimeric mouse model to study the protective role of two putative effector cell types, CD8+ T cells and a subpopulation of gamma/delta T cells that express WC-1, a member of the cysteine-rich scavenger receptor superfamily (CRSR). We demonstrate that CD8+ T cells play a key role in protection and contribute substantially to bovine IFN-gamma mRNA levels at 30 days post-infection. The role of WC-1 bearing cells to protection was less definitive but our results suggest that this population may play a pivotal role early in infection. Granuloma architecture was altered in anti-WC-1 (ILA29) but not anti-CD8 (ILA51) -treated animals, suggesting that this population may be involved in recruitment of various cell types to sites of infection.

Animals↗

PubMed1990

Lyme carditis in immunodeficient mice during experimental infection of Borrelia burgdorferi.

Recently, we described the severe combined immunodeficiency (scid) mouse as a laboratory model for B. burgdorferi infection. Scid mice inoculated with the virulent low-passage tick isolate Borrelia burgdorferi ZS7 developed a severe pancarditis involving endocardium, myocardium and epicardium in the absence of functional B- or T-cells. Soon after inoculation perivascular infiltration was observed, later diffuse infiltration of the interstitium of the subendocardial and subepicardial areas was seen. The infiltrate was mainly mononuclear and predominantly composed of Mac-1+ cells. Concomitantly, fibroblast proliferation and augmented collagen deposition occurred in the interstitium. This was associated with the presence of B. burgdorferi organisms. The histopathological and ultrastructural findings observed in scid mice resemble those observed in human Lyme carditis. The data emphasize the suitability of the scid mouse as a model in which to study the role of the immune system in the pathogenesis of Lyme carditis.

Animals↗

PubMed1993

Engraftment of human synovium into severe combined immune deficient mice. Migration of human peripheral blood T cells to engrafted human synovium and to mouse lymph nodes.

To determine the feasibility of using the C.B-17 scid/scid (severe combined immune deficient, SCID) mouse as a recipient of human synovial xenografts, we have engrafted human synovium under the renal capsule of SCID mice, and determined synovial graft survival and histologic characteristics 4 to 7 wk after tissue implantation. Both normal and inflammatory synovial tissue grew well in SCID mice and maintained histologic and phenotypic components of the fresh synovial tissue before implantation. However, the number of T cells in synovial grafts decreased after implantation. To determine whether leukocytes could migrate to human synovial xenografts, either allogenic or autologous PBMC were injected in the peritoneum of SCID mice bearing synovial xenografts. We found that 7 days after i.p. injection of autologous or allogeneic PBMC, injected T cells had selectively migrated to human synovial grafts and to SCID mouse lymph nodes. Our data demonstrate that normal and inflammatory human synovial tissues will grow in SCID mice and serve as recipients for autologous and allogenic peripheral blood human T cells injected i.p. into engrafted mice.

Aged↗