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PubMed1993

The diversity of in-frame TCR delta chain transcripts in aging SCID mice.

From spleen, liver, bone marrow, and gut of old C.B-17 scid/scid (SCID) mice, TCR delta chain transcripts were amplified by the polymerase chain reaction (PCR) using V delta 1-, V delta 2-, V delta 3-, V delta 4-, V delta 5-, V delta 6-, and C delta-specific primers. Selectively amplified, TCR delta-chain-encoding cDNA from these organs of five old SCID mice was cloned, and 175 randomly selected clones were sequenced. In this panel, 44 distinct rearrangement events were detected, 82% (36/44) of which were in-frame. For V delta 2, V delta 4, V delta 5, and V delta 6, 34 in-frame transcripts were found in five old SCID mice. No potentially functional transcript containing V delta 3 was found and an unusual type of transcript containing the V delta 1 gene segment spliced directly in-frame to C delta was the predominant type of V delta 1 expression. Junctional diversity was evident in most sequenced clones indicating an extensive potential diversity of SCID-derived TCR delta chains. Identical transcripts were amplified from different organs of the same old SCID mouse. No organ-specific expression of V delta genes was evident. TCR delta chain transcripts could be neither amplified from young SCID mice nor from young SCID mice nor from young or old scid/scid nu/nu mice (bred on a BALB/c background). Hence, an apparently thymus-dependent development of oligoclonal populations of TCR delta+ cells is observed in old SCID mice.

Aging↗

PubMedDate not supplied

Modulation of the allergen-induced human IgE response in Hu-SCID mice: inhibitory effect of human recombinant IFN-gamma and allergen-derived lipopeptide.

We have previously established a model to study the in vivo human IgE response using humanized SCID mice. Allergic SCID mice were obtained following intraperitoneal injection with mononuclear cells from Dermatophagoides pteronyssinus (Dpt)-sensitive patients, and sensitization by Dpt allergen intraperitoneal injection (immunization) or Dpt aerosol (inhalation). Human serum IgE was measured in allergic SCID mice after administration of human recombinant IFN-gamma or the lipopeptide LP 52-71 (derived from peptide p52-71 from Der p 1, Dpt major allergen, coupled to a lipophilic moiety), during the immunization or the inhalation phase. IFN-gamma inhibited human IgE production when given at the time of immunization, but not during inhalation. This effect was long-lasting as Dpt aerosol, given one month after immunization and IFN-gamma administration, failed to increase IgE levels. Unlike Dpt or p52-71, LP 52-71 failed to induce human IgE production at day 14 and 21 after its injection, but did inhibit the development of the IgE response after a secondary Dpt-challenge. Moreover, LP 52-71 administration 14 days after Dpt inhalation decreased IgE levels, in contrast to peptide 52-71, which increased IgE levels. Thus, taken together these results indicate that the development of the human IgE response in allergic SCID mice can be modulated by modified allergen and a Th1 cytokine.

Animals↗

PubMed1996

Immunoresponses of humanized SCID mice to human lung cancer cells.

HuPBL-SCID mice were used to explore how they would response to human tumor cells of 801/MLC. Living 801/MLC cells appeared to be fetal to the the mice due to the production of human TNF. The huPBL-SCID mice did not generate any noticeable amount of specific human immunoglobulin either by single immunization with living 801/MLC cells or by repeated immunization with irradiated 801/MLC cells. Our preliminary experiments with huPBL-SCID mice showed that such chimeras would be a very useful models for tumor immunological researches.

Animals↗

PubMed1993

Establishment and characterization of the tumors of chronic lymphocytic leukemia cell line in nude and SCID mice.

A new cell line, designated MO1043, was established from the peripheral blood (PB) of a patient with B-cell chronic lymphocytic leukemia (CLL). Both the PB leukemia cells and MO1043 were found to have an abnormal cytogenetic marker of trisomy 12, the most common cytogenetic abnormality in CLL. In addition, both the PB cells and MO1043 expressed a cell surface phenotype of typical B-CLLs. The MO1043 was efficiently transplanted into X-irradiated athymic nude mice by i.p. inoculation after it was subjected to serial passages in new born (1 week old) and irradiated adult nude mice. The tumor of a CLL cell line (termed CLL tumor) was also generated in the nude mice by s.c. inoculation of the cells. The MO1043 was inoculated i.p. into mice with severe combined immunodeficiency (SCID) which had not been subject to any preconditionings. The CLL tumor in the non-conditioned SCID mice was disseminated to various tissues in a manner more analogous to CLL tumors in patients as compared with nude mice, where the CLL tumors were not as widely disseminated. At each of four different tumor doses, i.e. 2 x 10(6), 6 x 10(6), 1.8 x 10(7) and 5.4 +/- 10(7) cells of MO1043, the transplantability was 100%. Titration experiments revealed a reciprocal relationship between survival and the number of tumor cells inoculated. FACS analysis showed that several cell surface markers of the parental MO1043 were maintained in CLL tumors from nude and SCID mice. Fluorescence in situ hybridization with novel DNA probes demonstrated that CLL tumors of both nude and SCID mice maintained trisomy 12. The CLL tumor models developed here, particularly the SCID mouse model, may be very useful for therapeutic studies of CLL.

Aged↗

PubMed1995

A method for rapid and complete substitution of the circulating erythrocytes in SCID mice with bovine erythrocytes and use of the substituted mice for bovine hemoprotozoa infections.

We have previously developed an in vivo experimental system for a bovine hemoprotozoan parasite, in which SCID mice were periodically transfused with bovine red blood cells (Bo-RBCs), followed by infection with the parasite. The SCID mice prepared by the original method, however, had both mouse and bovine RBCs in the circulation, and their proportion always fluctuated significantly. In the present study, we aimed to deplete the mouse RBCs circulating in SCID mice and, thereby, to create SCID mice having complete Bo-RBC substitution. An anti-erythropoietin rabbit serum, an anti-mouse RBC rabbit serum and 23 monoclonal anti-mouse RBC rat antibodies were prepared for this purpose. They were examined, after administration into SCID mice, for their ability to decrease hematocrit value and also for any other adverse effect. A monoclonal antibody, clone 2E11, was found to have potent ability to induce clearance of the mouse RBCs in SCID mice without causing toxic effects. SCID mice receiving this antibody together with periodic transfusion of Bo-RBCs had their circulating RBCs completely substituted with Bo-RBCs. Infection of Bo-RBC-SCID mice with bovine hemoprotozoan parasites demonstrated that elimination of the mouse RBCs from Bo-RBC-SCID mice resulted in augmentation of parasite growth.

Anemia↗

PubMed1995

Lol p I-specific IgE and IgG synthesis by peripheral blood mononuclear cells from atopic subjects in SCID mice.

BACKGROUND: The development of an animal model representative of the in vivo situation of human atopic diseases is always of interest for a better understanding of IgE production and regulation. Along these lines, mice with severe combined immunodeficiency (SCID mice) engrafted with lymphocytes from atopic subjects might be a suitable model for such studies. OBJECTIVE: This study aims to analyze the production of Lol p I-specific IgE and IgG antibodies in SCID mice after transplantation of human peripheral blood mononuclear cells from atopic patients sensitive to grass pollens and from nonatopic donors. METHODS: Peripheral blood mononuclear cells were transplanted into SCID mice, which were then challenged with Lol p I, and antibody responses (IgG and IgE) were analyzed over a 6-week period. RESULTS: Total IgG antibody was measured in each mouse serum after transplantation. Also, most mice (regardless of whether donors were atopic) that were challenged with Lol p I produced specific IgG antibody. Total IgE antibody production was observed only in mice grafted with cells from atopic patients. Lol p I-specific IgE antibodies were also produced after immunization with Lol p I. Although IgG antibody/response tended to plateau, the IgE antibody response increased until it peaked and declined thereafter. Interferon-gamma was detected in sera from mice producing IgE antibody, which supports a possible role of interferon-gamma in the decrease of IgE response. CONCLUSION: This study suggests that the SCID mouse model could represent an interesting approach to studying specific, total IgG and IgE antibody production, and ultimately their regulation.

Allergens↗

PubMed1992

Enhanced clearance of lactic dehydrogenase-5 in severe combined immunodeficiency (SCID) mice: effect of lactic dehydrogenase virus on enzyme clearance.

The lactic dehydrogenase (LDH) level in plasma and the clearance of LDH in C.B-17 scid (severe combined immunodeficiency; SCID) mice were compared with those in C.B-17 or BALB/cCrSlc mice with or without lactic dehydrogenase virus (LDV) infection. The resting enzyme level in SCID mice showed little difference from that in C.B-17 or BALB/cCrSlc mice. The degree of increased plasma LDH level in SCID mice was lower than that in C.B-17 and BALB/cCrSlc mice after LDV infection. To assess the mechanisms of decrease in LDH elevation in SCID mice infected with LDV, virus replication was compared in SCID and BALB/cCrSlc mice. The infectivity titre of plasma in SCID mice was higher (more than 10 times) than that in BALB/cCrSlc mice. Moreover, the percentage of virus antigen positive Kupffer cells was higher in SCID mice than that in BALB/cCrSlc mice. The level of endogenous LDH release as a result of carbon tetrachloride treatment was similar in the SCID and BALB/cCrSlc mice. The clearance rate of endogenous LDH was greater in SCID mice than in BALB/cCrSlc mice with or without LDV infection. The rate of clearance of intravenously injected porcine LDH-5, but not porcine LDH-1, was enhanced in SCID mice as compared with that in BALB/cCrSlc mice. Furthermore, carbon clearance was higher in SCID mice than that in BALB/cCrSlc mice. These results suggest that the smaller increase of plasma LDH after infection might be due, at least in part, to the enhanced LDH-5 clearance function by macrophages in SCID mice.

Animals↗

PubMed1999

Murine splenocytes induce severe gastritis and delayed-type hypersensitivity and suppress bacterial colonization in Helicobacter pylori-infected SCID mice.

The goal of this study was to evaluate the role of host immunity in gastritis and epithelial damage due to Helicobacter pylori. Splenocytes from H. pylori-infected and uninfected C57BL/6 mice were adoptively transferred to H. pylori-infected and uninfected severe combined immunodeficient (SCID) mice. Transfer was verified by flow cytometry, and all mice were evaluated for the presence of delayed-type hypersensitivity (DTH) by footpad inoculation with sterile H. pylori sonicate and for humoral immunity by enzyme-linked immunosorbent assay. The severity of gastritis and gastric epithelial damage was quantified histologically, epithelial proliferation was determined by proliferating cell nuclear antigen staining, and colonization was quantified by culture. C57BL/6 mice, but not nonrecipient SCID mice, developed moderate gastritis in response to H. pylori. In contrast, recipient SCID mice developed severe gastritis involving 50 to 100% of the gastric mucosa and strong DTH responses not present in C57BL/6 mice. DTH, but not serum anti-H. pylori immunoglobulin G, correlated with adoptive transfer, gastritis, and bacterial clearance. Severe gastritis, but not bacterial colonization, was associated with epithelial metaplasia, erosions, and an elevated labeling index. This study demonstrates that (i) adaptive immunity is essential for development of gastritis due to H. pylori in mice, (ii) T-cell-enriched lymphocytes in SCID mice induce DTH and gastritis, which is more severe than donor gastritis, and (iii) the host inflammatory response, not direct bacterial contact, causes epithelial damage. The greater severity of gastritis in recipient SCID mice than in donor C57BL/6 mice suggests that gastritis is due to specific T-cell subsets and/or the absence of regulatory cell subsets in the transferred splenocytes.

Adoptive Transfer↗

PubMed1995

Effect of surface antigen-1 (SA-1) immune lymphocyte subsets and naive cell subsets in protecting scid mice from initial and persistent infection with Cryptosporidium parvum.

We tested the hypothesis that adoptive transfer of immune spleen cell subsets from Cryptosporidium parvum antigen immunized, immunocompetent BALB/c mice would prevent initial infection or terminate persistent infection in severe combined immunodeficient (scid) mice. Cell donor mice were immunized with either solubilized C. parvum oocysts and sporozoites (positive control) or a surface antigen-1 (SA-1) enriched C. parvum antigen fraction. Both groups of BALB/c cell donor mice immunized with C. parvum antigens had increased antibody titers and lymphoproliferative responses when compared with negative control mice injected with phosphate buffered saline and adjuvant. Intravenous adoptive transfer of 5 x 10(6) cells of each cell subset (spleen cells, CD4 T and B lymphocytes, CD4 T lymphocytes or B lymphocytes) derived from immunized adult BALB/c donor mice did not protect scid mice against initial infection of the gastrointestinal epithelium with C. parvum, despite flow cytometric evidence of CD4 T lymphocyte engraftment in the spleen and detectable levels of C. parvum-specific serum antibody. In contrast, intravenous injection of either naive or immune CD4 T and B lymphocytes combined, or CD4 T lymphocytes alone, terminated persistent C. parvum infection in scid mice. Intestinal infectivity scores were significantly reduced by 9 days post-engraftment in all groups and continued to decline throughout the remainder of the experiment. Flow cytometric analysis demonstrated significantly increased CD4 T lymphocytes in the spleens of recipient scid mice when compared with infected scid mice receiving no cells. Cryptosporidium parvum-specific antibody was detected on day 12 post engraftment in mice receiving SA-1 immune CD4 T and B lymphocytes but was not detectable in mice receiving naive cell subsets.

Animals↗

PubMed1994

[The immune reconstitution in Scid mice and the effect of T, B, NK cells on the growth potential of CNE-2Z-H5 transplanted tumor].

CNE-2Z-H5 was transplanted into the Scid mice of which immune system was reconstituted with the peripheral lymphocytes or thymus of the isogenetic mice and the BALB/c nude mice of which NK cells were inhibited with cyclophosphamide. The results showed that the growth speed and weight of the tumors were in order from high to low among groups of Scid mice, BALB/c nude mice with NK inhibited, BALB/c nude mice, Scid mice with immune reconstitution. The transplanted tumor, in 6/6 cases injected beforehand with peripheral lymphocytes and 1/3 case transplanted accompanied with thymus disappeared within 22 days. The conclusion is that the immune reconstitution of Scid mice has succeeded and play an effective role in antitumor response.

Animals↗

PubMed1992

Herpes simplex virus type 1 mutant strain in1814 establishes a unique, slowly progressing infection in SCID mice.

Ocular infection of immunocompetent (BALB/c) mice with wild-type herpes simplex virus type 1 (HSV-1) 17+ may lead to acute fatal encephalitis; however, in surviving animals, a latent (nonproductive) infection of the nervous system is established. In contrast, 17+ infection invariably kills mice with severe combined immunodeficiency (SCID mice) within 2 weeks. Ocular infection of immunocompetent mice with a mutant HSV-1 strain, in1814, which does not produce a functional alpha-transinducing protein, results in no detectable viral replication in the nervous system during the time corresponding to the acute phase of infection, no mortality, and the establishment of latency. In SCID mice, however, the in1814 virus establishes a unique, slowly progressing infection. In studying the courses of in1814 infection in SCID and BALB/c mice, we found that although intact B- and/or T-lymphocytic functions were required for the control of viral replication in the nervous system, some of the infected neurons of SCID mice seemed to be able to restrict in1814 replication and harbor the virus in a latent state.

Animals↗

PubMed2000

Regulation of human cell engraftment and development of EBV-related lymphoproliferative disorders in Hu-PBL-scid mice.

Human PBMC engraft in mice homozygous for the severe combined immunodeficiency (Prkdcscid) mutation (Hu-PBL-scid mice). Hu-PBL-NOD-scid mice generate 5- to 10-fold higher levels of human cells than do Hu-PBL-C.B-17-scid mice, and Hu-PBL-NOD-scid beta2-microglobulin-null (NOD-scid-B2mnull) mice support even higher levels of engraftment, particularly CD4+ T cells. The basis for increased engraftment of human PBMC and the functional capabilities of these cells in NOD-scid and NOD-scid-B2mnull mice are unknown. We now report that human cell proliferation in NOD-scid mice increased after in vivo depletion of NK cells. Human cell engraftment depended on CD4+ cells and required CD40-CD154 interaction, but engrafted CD4+ cells rapidly became nonresponsive to anti-CD3 Ab stimulation. Depletion of human CD8+ cells led to increased human CD4+ and CD20+ cell engraftment and increased levels of human Ig. We further document that Hu-PBL-NOD-scid mice are resistant to development of human EBV-related lymphoproliferative disorders. These disorders, however, develop rapidly following depletion of human CD8+ cells and are prevented by re-engraftment of CD8+ T cells. These data demonstrate that 1) murine NK cells regulate human cell engraftment in scid recipients; 2) human CD4+ cells are required for human CD8+ cell engraftment; and 3) once engrafted, human CD8+ cells regulate human CD4+ and CD20+ cell expansion, Ig levels, and outgrowth of EBV-related lymphoproliferative disorders. We propose that the Hu-PBL-NOD-scid model is suitable for the in vivo analysis of immunoregulatory interactions between human CD4+ and CD8+ cells.

Adoptive Transfer↗

PubMed1992

Differential kinetics of engraftment and induction of CD10 on human pre-B leukemia cell lines in immune deficient scid mice.

The sensitivity of the scid mouse model was assessed by comparing the growth of two pre-B acute lymphoblastic leukemia (ALL) cell lines, A1 and G2, established from patients at relapse. When cell numbers varying from 10(4) to 10(7) were injected intravenously into scid mice, advanced growth and dissemination of leukemia was observed at 10-12 weeks with the G2 cells. Bone marrow, spleen and thymus contained high levels of human leukemic cells and infiltration into lung, kidney, liver, and brain was observed. Two of three mice grafted with only 100 cells showed high levels of infiltration at 15 weeks, suggesting that 100 G2 cells was near the limiting cell number that could produce disseminated leukemia. With the A1 line, a minimum of 10(5) cells was needed to obtain dissemination to liver, lung, brain, and kidney; a low level of spleen infiltration occurred and thymus invasion was not observed. In vitro, both lines showed a density dependent growth in clonogenic assays but the cloning efficiency of the A1 line was 10-fold higher than for G2 cells. These results indicate that G2 and A1 lines have a dissimilar aggressiveness in vivo which does not correlate with clonogenic assay in vitro. Neither G2 nor A1 lines, growing in vitro, expressed CD10/CALLA on their surface, despite low levels of antigen on the freshly obtained relapse samples. Although A1 cells remained CD10-negative in the scid mice, G2 cells showed detectable levels of CD10, particularly on those cells found in the thymus. Several subclones of the G2 line were derived from isolated colonies in vitro; they were found to be CD10- in vitro, but to become CD10+ when proliferating into scid mouse thymus, suggesting the induction of CD10 by the murine microenvironment.

Animals↗

PubMed1999

Effects of recombinant human erythropoietin on the antitumor effect of cisplatin in SCID mice bearing human ovarian cancer: A possible oxygen effect.

PURPOSE: Experiments were designed to evaluate the effect of an elevated hematocrit using recombinant human erythropoietin (Epo) on the antitumor response of cisplatin on human ovarian cancer engrafted in mice. METHODS: Forty female severe combined immunodeficient (SCID) mice with large human ovarian cancer xenografts implanted on the gonadal fat pad (GFP) and 40 female SCID mice with small subcutaneous (sq) human ovarian cancer xenografts were placed in one of four treatment groups. Group 1 (controls) received phosphate-buffered saline injections. Group 2 (Epo group) received Epo at 20 units three times per week. Group 3 (cisplatin group) received cisplatin at 5 mg/kg/week. Group 4 (Epo + cisplatin group) received Epo and cisplatin as above. Cisplatin was administered on day 0 for mice bearing large GFP tumors and was injected on days 0 and +7 for mice bearing small sq tumors. Epo injections were started on day -15 and continued until the completion of the experiment. Evaluations of the tumor growth, hematocrits, and performance status were made. The experiments were repeated in 24 SCID mice bearing small sq tumor xenografts with similar results. Representative data were reported. RESULTS: Among mice bearing large GFP tumors, a tumor growth delay was noted in the groups that received cisplatin with or without Epo compared to controls (P < 0.05). However, significant tumor growth delay could not be reached for mice in the Epo + cisplatin group compared to the cisplatin group (P = 0.07). Among mice bearing small sq tumors, a significant improvement in tumor regression was achieved in the Epo + cisplatin group compared to the cisplatin group (P < 0.05). No difference in tumor growth resulted in the Epo group compared to controls. Epo resulted in a 25-35% increase in the hematocrit in both the Epo group and the Epo + cisplatin group (P < 0.01). Mice in the control and in the Epo groups remained healthy. Mice treated with cisplatin developed objective signs of morbidity; however, performance scores for mice in the Epo + cisplatin group remained lower than scores in the cisplatin group. CONCLUSIONS: The data demonstrate a cisplatin-sensitizing effect on human ovarian cancer in SCID mice induced by the pretreatment elevation and maintenance of the hematocrit using Epo. These findings are consistent with an oxygen sensitization of cisplatin. Corroboration of these results may have significant clinical implications for the treatment of solid tumor patients.

Animals↗

PubMed1996

Dextran sulfate sodium (DSS) induced experimental colitis in immunodeficient mice: effects in CD4(+) -cell depleted, athymic and NK-cell depleted SCID mice.

Administration of dextran sulfate to mice, given in the drinking water results in acute or subacute colonic inflammation, depending on the administration protocol. This colonic inflammation exhibits ulceration, healing and repair, and a therapeutic response that makes it valuable for the study of mechanisms that could act in the pathogenesis of human ulcerative colitis, a disease thought to have an immunologically dependent pathogenesis. To investigate if immunological mechanisms were involved in the induction of colonic inflammation in this model, mice with different degrees of immunodeficiency were used. It was shown that dextran sulfate induced colitis could be induced in Balb/c mice depleted of CD4(+) helper T cells by treatment with monoclonal antibodies preceded by adult thymectomy. The depletion of CD4(+) was verified by flow cytometric analysis. Furthermore, the colonic inflammation could equally be induced in athymic CD-1 nu/nu mice lacking thymus-derived T cells, in T and B-cell deficient SCID mice, and also in SCID mice depleted of NK cells by treatment with anti-asialo GM1 antibodies. The NK-cell depletion was verified by measuring spleen NK-cell activity. The resulting colonic inflammation in all these types of deficient mice was qualitatively comparable, as shown by clinical and histological appearance. These results indicate that the presence of functional T, B and NK cells is not crucial for the induction of dextran sulfate colitis in mice.

Administration, Oral↗

PubMed1998

T lymphocytes are not the target for estradiol-mediated suppression of DTH in reconstituted female severe combined immunodeficient (SCID) mice.

Oestrogen has the capacity to suppress T cell-dependent DTH. To explore the mechanisms whereby oestrogen exerts its effects on the immune system we have used SCID mice which are largely devoid of functional T and B lymphocytes, hence being unable to raise DTH, but display intact antigen-presenting capacity. Transfer of lymphocytes to SCID mice restores the DTH capacity. In order to analyse if oestrogen down-regulates DTH by a direct action on T cells we reconstituted SCID mice with either splenocytes or thymocytes from congenic C.B-17 or allogeneic B6 donor mice. Either donor or recipient mice were exposed to estradiol before cell transfer. DTH response was registered in recipient SCID mice 1 and 3 weeks after challenge with oxazolone (OXA). SCID mice receiving estradiol-exposed spleen cells from congenic or allogeneic donor mice displayed lower DTH responses compared with control mice. In contrast, SCID mice receiving estradiol-exposed thymocytes from congenic donor mice showed no significant difference in DTH response compared with control mice. Estradiol-treated SCID mice, transferred with either spleen cells or thymocytes from congenic, hormonally non-treated donors, displayed a significantly lower DTH response compared with control mice. In contrast, estradiol-treated SCID mice receiving hormonally non-treated allogeneic spleen cells showed no difference in DTH response compared with control mice. The results show that T lymphocytes are not the target cell population for estradiol-mediated suppression of DTH in reconstituted female SCID mice.

Adjuvants, Immunologic↗

PubMed1992

Effect of donor and recipient immunization protocols on primary and secondary human antibody responses in SCID mice reconstituted with human peripheral blood mononuclear cells.

We have examined the ability of mice with severe combined immunodeficiency (SCID mice) reconstituted with human peripheral blood mononuclear cells (PBMC) to generate human antibody responses after specific immunization. SCID mice reconstituted with cells from a keyhole limpet hemocyanin (KLH)-naive donor are unable to generate specific human antibody responses after immunization with that antigen. After KLH immunization, SCID mouse recipients of human PBMC from a KLH-immune subject develop specific human antibody levels exceeding those of the donor. Human antitetanus antibody titers in reconstituted, immunized mice are also equivalent to those of the donor, provided that the mice are immunized within days of human cell transplantation. The ability of reconstituted mice to generate high titers of specific human antibody is lost within 35 days of human cell reconstitution, even though titers of total human immunoglobulin (Ig) are preserved. SCID mice reconstituted with tetanus-immune donor cells fail to generate IgA responses after booster immunization, and IgM responses are low or nonexistent. These data indicate that early exposure of the adoptive recipients of human cells to antigen is required to transfer specific human humoral responses. These findings are also consistent with a requirement for persistence of antigen for the maintenance of B-cell memory. The ability to achieve specific human antibody levels equivalent to those obtained with humans indicates that reconstituted mice may be useful for the evaluation of human antibody-mediated mechanisms of resistance to infection. The data indicate, however, that cells from immunized donors will have to be used for such studies.

Animals↗

PubMed1996

Replication of scrapie in spleens of SCID mice follows reconstitution with wild-type mouse bone marrow.

SCID mice are resistant to intraperitoneal infection with 10(3) and 10(4) intracerebral ID50 units of ME7 scrapie agent whereas they develop disease after intracerebral challenge. However, higher doses introduced, by intraperitoneal or subcutaneous routes, produce disease. Immunocompetent mice of the same strain (CB20) developed scrapie following either intracerebral or intraperitoneal infection. Bioassay of spleens from SCID mice infected with 10(-1) dilutions of ME7 scrapie by intraperitoneal, intracerebral or abdominal subcutaneous injection showed traces or low levels of infectivity in spleen. However, subcutaneous injection beneath the skin of the neck failed to infect the spleen. CB20 bone marrow reconstitution of SCID mice resulted in the regeneration of a normal lymphoid architecture in the spleen. Spleens from these reconstituted mice, infected intracerebrally with a 10(-1) dilution of ME7 contained high levels of infectivity. These results suggest that the ability to replicate scrapie agent in spleen or lymphoid tissue depends on the restoration of normal lymphoid structure and in particular the presence of differentiated follicular dendritic cells. The possibility that SCID mice can select minor strains of scrapie which are normally unrecognized in cloned ME7 is discussed.

Animals↗