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Results for “Mice, SCID”

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PubMed1994

The in vivo production of specific human antibodies by vaccination of human-PBL-SCID mice.

Human-PBL-SCID animals were created by intraperitoneal (i.p.) transfer of human peripheral blood lymphocytes (PBL) or PBL depleted of CD8-expressing lymphocytes (CD8dL). Analysis of human immunoglobulin levels in these animals revealed that severe combined immunodeficiency (SCID) mice receiving CD8dL produced significantly higher levels of serum human immunoglobulin than those receiving PBL. In an attempt to induce antigen-specific human antibodies these human-PBL-SCID animals were vaccinated with soluble protein antigen [ovalbumin (OVA)] entrapped within liposomes as an immunological adjuvant. Vaccination produced antigen-specific human IgM and IgG in human-PBL-SCID mouse serum. The use of liposomes as adjuvant and the reconstitution of animals with CD8dL together enhanced the OVA-specific immune response as evidenced by the detection of significantly increased serum antibody titres. In the CD8dL reconstituted group, solid tumours of human B-cell origin became detectable in the peritoneal cavity of animals at 8-10 weeks post-reconstitution. These tumours were readily established in vitro and subsequent analysis of culture supernatants showed that these malignant cells continue to secrete human antibodies specific for the original immunizing antigen in vitro. We believe this vaccination of the human-PBL-SCID mouse to produce antigen-specific human antibodies, may find use in the future production of human monoclonal antibodies and in the testing and development of novel vaccine/adjuvant systems.

Adjuvants, Immunologic↗

PubMed1997

Regulation of experimental autoimmune orchitis by the presence or absence of testicular antigens during immunological development in SCID mice reconstituted with fetal liver cells.

Severe combined immunodeficient (SCID) mice were immunologically reconstituted by the transfer of fetal liver cells (FLC) of BALB/c mice (SCID-FLC mice). In peripheral blood (PB) of SCID-FLC mice, B and T cells started to appear 2 and 5 weeks, respectively, after the transfer of FLC, and had attained normal levels by 7 weeks. Orchidectomy and transplantation of testis under the kidney capsule were conducted at various stages of immunological maturation, and the induction of experimental autoimmune orchitis (EAO) was performed after immunological maturation in SCID-FLC mice. The experimental system was used to establish that the presence of testicular antigens in the early stage of immunological development influences the induction of EAO; grade of EAO was reduced in the presence of the antigens, and enhanced in their absence. In other words, the existence of self tissue antigens in the early stage of immunological development was essential for proper establishment of tolerance to the self tissue. These findings suggested that the SCID-FLC mouse is a suitable model with which to analyse the interaction between self antigens and cells of the developing immune system, which is otherwise observed only in the fetal or perinatal stage in experimental animals.

Animals↗

PubMed2003

CD4+ T regulatory cells from the colonic lamina propria of normal mice inhibit proliferation of enterobacteria-reactive, disease-inducing Th1-cells from scid mice with colitis.

Adoptive transfer of CD4+ T cells into scid mice leads to a chronic colitis in the recipients. The transferred CD4+ T cells accumulate in the intestinal lamina propria (LP), express an activated Th1 phenotype and proliferate vigorously when exposed ex vivo to enteric bacterial antigens. As LP CD4+ T cells from normal BALB/c mice do not respond to enteric bacterial antigens, we have investigated whether colonic LP-derived CD4+ T cells from normal mice suppress the antibacterial response of CD4+ T cells from scid mice with colitis. LP-derived CD4+ T cells cocultured with bone marrow-derived dendritic cells effectively suppress the antibacterial proliferative response of CD4+ T cells from scid mice with colitis. The majority of these LP T-reg cells display a nonactivated phenotype and suppression is independent of antigen exposure, is partly mediated by soluble factor(s) different from IL-10 and TGF-beta, and is not prevented by the addition of high doses of IL-2 to the assay culture. Functionally and phenotypically the T-reg cells of the present study differ from previously described subsets of T-reg cells. The presence of T cells with a regulatory potential in the normal colonic mucosa suggests a role for these cells in the maintenance of local immune homeostasis of the gut.

Adoptive Transfer↗

PubMed1994

Loss of active neuroinvasiveness in attenuated strains of West Nile virus: pathogenicity in immunocompetent and SCID mice.

The neuropathogenicity of West Nile virus (WNV) and two derived attenuated strains WN25 and WN25A, was studied in young adult ICR mice and in severe combined immunodeficient (SCID) mice. Similarity in serology and RNA fingerprints were found between WNV and WN25. The viral envelope proteins of the attenuates differed from WNV in their slower mobility in SDS-PAGE due probably to the presence of N-linked glycan. The three strains were lethal to ICR mice by intracerebral (IC) inoculation, but when inoculated intraperitoneally (IP), WNV caused viremia, invaded the CNS and was lethal, whereas the attenuates showed no viremia or invasion of the CNS. The attenuates elicited antibodies to comparable levels as WNV in IP-infected mice, conferring upon them immunity to IC challenge with the wild type. In IP-inoculated SCID mice the three strains exhibited similar high viremiae that lasted until death of the animals. All strains invaded the CNS and proliferated in the mouse brain to similar high titers, but differed largely in the time of invasion: WNV invaded the CNS of SCID mice (and two other mouse strains) much earlier than the attenuates, which showed large intervals in their time of invasion into individual mouse brains within the group. The data presented for SCID mice indicate that WN25 and WN25A have truly lost the neuroinvasive property, and that this property materialized by a prescribed, active process specific for WNV.

Aedes↗

PubMed1988

Evidence of functional lymphocytes in some (leaky) scid mice.

Although the majority of severe combined immune deficiency (scid) mice lack functional lymphocytes, some (2-23%) appear to develop a limited number of B and T cells between 3 and 9 mo old. Most of these leaky scid mice were shown to contain very few clones (less than or equal to 3) of Ig-producing plasmacytes. Clonal progeny were distributed unevenly in the lymphatic tissues and appeared as discrete plasmacytic foci. In many cases, individual clones persisted for several months and produced abnormally high concentrations of Ig that included multiple isotypes. Functional T cells were inferred from the ability of leaky mice to reject allogeneic skin grafts, a T cell-dependent reaction. Interestingly, approximately 40% of leaky mice developed thymic lymphomas. In other respects, leaky mice resembled regular scid mice; e.g., their splenic cells failed to express common lymphocyte antigens (Ly-5[B220], Ly-1) and to proliferate in response to lymphocyte mitogens. Histologically, their lymphoid tissues retained the same general pattern of severe lymphocytic deficiency as scid mice.

Animals↗

PubMed1993

hu-PBL-SCID mice can be protected from HIV-1 infection by passive transfer of monoclonal antibody to the principal neutralizing determinant of envelope gp120.

OBJECTIVE: To determine whether passive transfer of a monoclonal antibody specific for the principal neutralizing determinant in the V3 region of HIV-1IIIB gp120 can protect mice with severe combined immunodeficiency (SCID) transplanted with normal human peripheral blood leukocytes (hu-PBL), designated hu-PBL-SCID mice, from subsequent challenge with the homologous viral strain. DESIGN AND METHODS: hu-PBL-SCID mice were given intraperitoneal injections of an anti-HIV-1 neutralizing murine monoclonal antibody (BAT123), its mouse-human chimeric form (CGP 47 439), or a control murine antibody (PNTU), at a dose of 40 mg/kg. The mice were then challenged intraperitoneally with 10 mouse infectious doses of HIV-1IIIB. Three weeks later the mice were killed, and spleen cells and peritoneal lavage collected for determination of infection by coculture for viral isolation and by detection of HIV-1 DNA using polymerase chain reaction (PCR). RESULTS: All three antibodies had similar serum half-lives of 9-12 days. No toxicity was observed in the animals. HIV-1 was recovered by coculture from five out of the six mice given PNTU, and by PCR from two out of the six mice given PNTU, but was not recovered by either technique from any of the 12 mice given BAT123 or CGP 47 439. CONCLUSION: BAT123 and CGP 47 439, which are specific for the principal neutralizing determinant of HIV-1IIIB, protect hu-PBL-SCID mice from infection by this viral strain. Our findings support the use of the hu-PBL-SCID mouse as an in vivo model for studying protection against HIV-1 infection by passive immunization with anti-HIV-1 neutralizing antibodies.

Animals↗

PubMed1992

Dynamics and localization of early B-lymphocyte precursor cells (pro-B cells) in the bone marrow of scid mice.

Mice homozygous for the scid (severe combined immunodeficiency) mutation are generally unable to produce B lymphocytes, a condition attributed to defective rearrangement of immunoglobulin genes in precursor B cells. Some early B-lineage cells are present in the bone marrow (BM), however. In scid mice, we defined three subsets of early progenitor B cells lacking mu heavy chains (pro-B cells) based on the expression of terminal deoxynucleotidyl transferase (TdT) and B220 glycoprotein: (a) early pro-B cells (TdT+B220-), (b) intermediate pro-B cells (TdT+B220+), and (c) late pro-B cells (TdT-B220+). Double immunofluorescence labeling of BM cell suspensions has shown normal numbers of early and intermediate pro-B cells, substantially reduced numbers of late pro-B cells, and an absence of pre-B cells and B cells. Early and intermediate pro-B cells accumulated in metaphase in near-normal numbers after intraperitoneal (IP) vincristine administration. B220+ pro-B cells have been localized in BM sections by the binding of intravenously (IV) administered 125I monoclonal antibody (MoAb) 14.8, detected by light and electron microscope radioautography. Many B220+ cells were located peripherally in the bone-lining cell layers associated with stromal reticular cells. More centrally located B220+ cells were frequently associated with macrophages containing prominent cytoplasmic inclusions. Occasional B220+ cells were present in venous sinusoids. These results demonstrate that many pro-B cells in scid mice occupy microenvironments in the BM near the surrounding bone. The pro-B cells maintain normal rates of production during stages of presumptive mu heavy-chain gene rearrangement, apparently unaffected by the absence of a mature B cell pool. Nearly all defective cells then abort at the late pro-B cell stage and are deleted, apparently by macrophages. The findings contribute to models of in vivo differentiation, regulation, localization, and selection of early B-lineage cells in the BM.

Animals↗

PubMed1993

Xenogeneic PBL-scid mice: their potential and current limitations.

The hu-PBL-scid has been constructed by intraperitoneal inoculation of lymphocytes from human peripheral blood into immunodeficient scid mice. Such scid mouse-human chimeras have proven useful as in vivo animal models for studies on human lymphocyte development and differentiation from pluripotent stem cells. Further, the hu-PBL-scid mouse provides a readily accessible model for the examination of immune cell function and involvement in autoimmune and infectious disease processes. In response to the growing need for model systems to examine the immune system and disease pathogenesis in agriculturally important animals, PBL engraftment of scid mice has expanded to include the bovine and equine species. This review discusses the properties and potential uses of the xenogeneic PBL-reconstituted scid mouse.

Animals↗

PubMed1995

Tetanus toxoid-specific T cell responses in severe combined immunodeficiency (SCID) mice reconstituted with human peripheral blood lymphocytes.

SCID mice reconstituted with human peripheral blood lymphocytes (PBL) have repeatedly been shown to produce antigen-specific B cell responses. We have derived tetanus toxoid (TT)-specific human T cell lines from cells of the peritoneal cavity, spleen and lymph nodes of SCID mice reconstituted with human PBL and boosted with TT. Establishment of these cell lines was dependent on the time interval between reconstitution of the mice with human PBL and initiation of lymphocyte cultures in vitro. When lymphocytes were collected from the mice 8 weeks after reconstitution, human lymphocytes with TT-specific proliferative activity in vitro were isolated from the peritoneal cavity and spleen, but long-term cell lines could not be established after repeated lymphocyte stimulation with TT, IL-2 and autologous Epstein-Barr virus-transformed B cells. In contrast, three long-term (> 10 months) TT-specific human T cell lines were established from lymphocytes collected from two of the eight mice in the group 4 weeks after reconstitution. The T cell lines were either CD4+ (two lines derived from peritoneal cavity and lymph node, respectively) or CD8+ (one line derived from spleen) and all expressed CD3, T cell receptor alpha/beta, and human histocompatibility leucocyte class I antigen. The T cell lines, however, lacked cytotoxic, helper and suppressor activities. Thus, SCID mice can support human T cells that actively migrate to various organs and respond to antigenic stimuli both in vivo and in vitro, but these T cells lack characteristic functions.

Animals↗

PubMed1996

Anti-CD45 and anti-CD52 (Campath) monoclonal antibodies effectively eliminate systematically disseminated human non-Hodgkin's lymphoma B cells in Scid mice.

Severe combined immunodeficient (Scid) mice inoculated with the human (t(14;18)-positive B cell lines DoHH2 and BEVA develop lethal systemically disseminated lymphoma (de Kroon et al., Leukemia 8:1385, and Blood 80 [suppl 1]:436). These models were used to study the therapeutic effect of rat-anti-human CD52 (Campath-1G) or CD45 monoclonal antibodies (mAbs) on systemically disseminated tumor cells and on tumor cells present in solid tumor masses. Both mAbs were effective in inhibiting growth of systemically disseminated malignant cells. When treatment with anti-CD52 or anti-CD45 mAbs at a dose of 30 micrograms/mouse/d for 4 days was started 24 hours after intravenous inoculation of human DoHH2 or BEVA cells, a 3-log kill of tumor cells was observed as measured by prolonged survival. After treatment, surviving animals injected with high numbers of BEVA cells showed tumor masses in liver, kidney, and mesenteric lymph nodes. In contrast to nontreated animals, however, only low numbers of malignant cells were found in peripheral blood, and bone marrow was free of tumor cells. Similarly, after mAb treatment of mice inoculated subcutaneously (sc) with DoHH2 cells, no tumor cells could be found in the bone marrow, and few DoHH2 cells could be detected in the peripheral blood, spleen, liver, kidney, or lung. In contrast, tumor cells present in subcutaneous tumors and axillary lymph nodes were relatively unaffected by mAb therapy. The presence of rat immunoglobulin (Ig) could be demonstrated on surviving tumor cells. The presence of murine macrophages in areas in these tumors that were depleted of DoHH2 cells suggested that the mAb-mediated antitumor effect observed in the Scid mouse model is mediated by cellular mechanisms. Apparently these mechanisms were not sufficient to eliminate the fast-growing tumor cells present in the protected sites. Our results indicate that treatment with anti-CD52 or anti-CD45 mAbs potentially may be useful as adjuvant immunotherapy for systemically disseminated B cell lymphoma.

Animals↗

PubMed1999

Type I interferon is a powerful inhibitor of in vivo HIV-1 infection and preserves human CD4(+) T cells from virus-induced depletion in SCID mice transplanted with human cells.

Although several studies are available on the in vitro inhibitory activities of type I interferon (IFN) on HIV-1 replication, the role of these cytokines in the pathogenesis of AIDS is still matter of conjecture. Both beneficial and adverse effects have been envisaged and considered as a possible rationale for the development of either IFN or anti-IFN therapies in HIV-1-infected patients. In the present study, we have evaluated the efficacy of human type I IFN on HIV-1 infection and virus-induced depletion of human CD4 T cells in two models established in SCID mice. In SCID mice transplanted with human U937 cells (U937-SCID mouse model), continuous treatment with type I consensus IFN (CIFN) resulted in a total suppression of HIV-1 infection. This inhibitory effect was superior to that obtained after AZT treatments. Results from an ensemble of experiments in SCID mice transplanted with either control or genetically modified human U937 cells transduced with a Tat-inducible IFN-alpha gene (LTR-IFN-A2 U937) indicated that low levels of IFN-alpha, produced locally as a result of virus infection, were extremely effective in inhibiting acute HIV infection and virus replication. Of interest, LTR-IFN-A2 U937 cells conferred a strong anti-HIV-1 protection to coinjected bystander U937 cells. Notably, experiments with SCID mice reconstituted with human PBL (hu-PBL-SCID mouse model) showed that treatment with CIFN inhibited HIV-1 replication more effectively than AZT treatment. Remarkably, treatment with CIFN resulted in a clear-cut protection from the virus-induced depletion of human CD4 T cells, which was also associated with the generation of an antibody response toward HIV-1 antigens in 50% of the virus-injected xenografts. These results suggest that type I IFN efficiently preserves human CD4(+) cells from virus-induced damage in hu-PBL-SCID mice, not only by inducing an antiviral state in target cells but also by stimulating anti-HIV-1 human immune responses in vivo.

Animals↗

PubMed2002

Cytokine gene expression by alloactivated cells in SCID mice.

OBJECTIVES: The severe combined immune deficient (SCID) mouse provides a neutral environment to study human immune responses. We therefore tested human gene expression of Interleukin (IL) 2, 4 and 10, interferon gamma (IFNgamma); transforming growth factor beta 1 (TGFbeta1); and CD40 ligand (CD40L) in splenic extracts of SCID mice after engraftment of PBLs from two persons (direct MLR) or one person plus allopeptides (indirect MLR) in the presence or absence of cyclosporin A (CsA) or FK506. METHODS: Cytokine gene expression was detected by RT and quantitative (for IFN-gamma, TGFbeta1 and CD40L) PCR. All cells, allopeptides, CsA (25 mg/kg/day for 7 days) or FK 506 (0.5 mg/kg/day for 7 days) were administered intraperitoneally (IP). RESULTS: In both direct and indirect MLR the numbers of SCID mice expressing the human cytokine genes varied between 33% for IL4 and 100% for IL10, IFN-gamma, TGFbeta1, and CD40L. There was significant interpersonal variation in levels of gene expression. Concomitant CsA or FK506 administration for 7 days did not abrogate early or late (1 week after discontinuation of CsA or FK506) cytokine gene expression in either the direct or indirect MLR, but paradoxically enhanced levels of IFN-gamma, TGFbeta1 and CD40L gene expression in some experiments. CONCLUSIONS: The results explain late rejection after rapid calcineurin inhibitor withdrawal or reduction, and illustrate the potential use of SCID mice as a surrogate model to study graft outcome by determination levels of gene expression and sensitivity to immunosuppressive agents in the in vivo alloresponse.

Animals↗

PubMed1993

Functional and phenotypic analysis of thymocytes in SCID mice. Evidence for functional response transitions before and after the SCID arrest point.

Thymocytes from severe combined immune deficient (SCID) mice undergo developmental arrest at an early stage, before most TCR gene rearrangement. They therefore represent a natural test case to assess those aspects of T cell development that are TCR independent. Multiparameter flow cytometry was used to analyze the array of immature phenotypes present in the SCID thymus at steady state, as defined by the markers CD4, CD5, Sca-1, NK1.1, CD44, heat-stable antigen (HSA), and IL-2R alpha. The results suggest a simple developmental block in SCID mice rather than a program of aberrant differentiation. SCID thymocytes displayed efficient, developmentally regulated functional responses. Approximately 20-25% of the cells, mostly within the IL-2R alpha +HSA+CD44low fraction, could be induced to express IL-2. This IL-2 inducibility was highly dependent on IL-1 costimulation, in agreement with the behavior of normal immature thymocytes. These results formally demonstrate that competence to express IL-2 is developed independently of TCR expression or gene rearrangement. Comparison of the response properties of various SCID thymocyte subsets indicated that IL-2 inducibility is first likely to be acquired at an early (Sca-1++CD44++HSAlow) stage. A later functional transition was revealed by comparing patterns of IL-2R alpha regulation in normal and SCID IL-2R alpha +HSA+CD44low thymocytes. The SCID thymocytes uniformly maintained IL-2R alpha expression on in vitro stimulation, whereas only a minority of the normal cells in the corresponding subset could do so unless IL-1 was also added. The SCID arrest point thus appears to separate the IL-2R alpha +HSA+CD44low stage into distinct early (TCR independent) and late phases. Normal cells that progress beyond the SCID arrest point appear to lose, rather than gain, competence to make various responses, even before they leave the IL-2R alpha +HSA+CD44low stage. A model is proposed in which discrete changes in functional competence define novel transitions in early thymocyte development, at least some of which may be linked to TCR-beta gene rearrangement before positive or negative selection.

Animals↗

PubMed1993

Comparative abilities of athymic nude mice and severe combined immune deficient (SCID) mice to accept transplants of induced rat mammary carcinomas: enhanced transplantation efficiency of those rat mammary carcinomas that have elevated expression of neu oncogene.

Grafts of primary carcinogen (DMBA)-induced mammary carcinomas from Sprague-Dawley rats have a poor transplantation efficiency in athymic nude mice. Further compromising these mice immunologically via whole-body irradiation and/or splenectomy, or the administration of hormonal growth factors (estrogen and progesterone) to these mice, did not significantly alter transplantation efficiency. Use of strains of mice that are more immune-impaired than the athymic nude mouse, i.e., the athymic nude-beige-XID mouse (T-cell and LAK-cell deficient) or mice with severe combined immune deficiency (SCID) (which lack functional T cells and B cells) also failed to improve transplantation efficiency. In contrast, transplantation efficiency was sharply increased when primary neu-induced rat mammary carcinomas from female Sprague-Dawley rats were used. These mammary carcinomas, unlike the DMBA-induced rat mammary carcinomas, have a very high level of expression of neu; transplantation of these tumors to either athymic nude mice or SCID mice was considerably more efficient. Thus, these data provide evidence that enhanced expression of neu confers heightened efficiency in the transplantation of primary rat mammary carcinomas to immune-deficient mice (athymic-nude or SCID). Increased neu expression was a greater determinant than more compromised immune states in the transplantation of these rat mammary carcinomas. This biological characteristic of neu expression in mammary carcinomas provides new, additional insight into the importance of this oncogene in mammary tumorigenic processes and may explain, at least in part, the reported inverse relationship between human breast carcinoma neu expression and patient prognosis.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1994

Antibodies to the serine rich Entamoeba histolytica protein (SREHP) prevent amoebic liver abscess in severe combined immunodeficient (SCID) mice.

Amoebic liver abscess caused by Entamoeba histolytica is a major cause of morbidity and mortality worldwide. We used mice with severe combined immunodeficiency (SCID mice) to study the role of antibody in protection from amoebic liver abscess, and to identify protective antigens of E. histolytica. Antisera to recombinant versions of two major surface antigens of E. histolytica, the serine rich E. histolytica protein (SREHP) and the 170 kDa adhesin were used in this study. We found that 100% of SCID mice passively immunized with antiserum to the recombinant SREHP molecule were protected from developing amoebic liver abscess after intrahepatic challenge with virulent E. histolytica trophozoites. In contrast, preimmune serum, antiserum to a portion of the 170 kDa adhesin, and antiserum to the trpE fusion partner of SREHP did not protect SCID mice from amoebic liver abscess. Our study demonstrates that antibodies to a recombinant version of the amoebic SREHP molecule can protect against amoebic liver abscess, and suggest the recombinant SREHP molecule should be considered as a possible vaccine candidate to prevent amoebic liver abscess.

Animals↗

PubMed2006

Development of functional B cells in a line of SCID mice with transgenes coding for anti-double-stranded DNA antibody.

Deletion or inactivation of anti-self (DNA) B cells has been reported in non-autoimmune mice bearing Ig transgenes that code for Abs with specificity for dsDNA or ssDNA. However, we report a case in which anti-dsDNA B cells appear to escape both deletion and inactivation. We show that B cells (B220+IgM+) can develop in non-autoimmune SCID mice bearing two site-directed transgenes, 3H9(56R) and Vkappa8, that together code for an anti-dsDNA Ab. The B cells appear inactive, because the mice (56RVkappa8 SCID mice) generally lack serum Ig. However, 56RVkappa8 SCID mice are able to produce IgG Ab with specificity for dsDNA when they become "leaky" for T cells or are reconstituted with exogenous T cells from B cell-deficient JH-/- donors. Thus, anti-dsDNA B cells that escape deletion in 56RVkappa8 SCID mice appear fully functional and can differentiate, class switch, and give rise to IgG-producing cells in the presence of T cells and self-Ag.

Animals↗

PubMed1997

Human cytotoxic CD8+ T-lymphocyte clones engraft in severe combined immunodeficient (SCID) mice but show diminished function.

Mice with severe combined immunodeficiency (SCID) provide an in vivo model for studying interactions between human tumor cells and effector cells of the immune system. We studied the behavior of human alloreactive cytotoxic T lymphocytes (CTLs) in SCID mice, including the migration pattern of CD8+ or CD4+ CTL clones to various murine tissues, their engraftment in the absence or presence of recombinant human interleukin 2 (rhIL-2) compared with the engraftment of lymphokine activated killer (LAK) cells, and the in vitro as well as the in vivo function of the engrafted CTL clones. The polymerase chain technique using T-cell-receptor-gamma specific primers revealed the presence of human CD8+ CTL clones in the blood, lungs, and liver of mice receiving rhIL-2 for 14 days, for at least 18 days after intravenous inoculation. Human T cells were transiently detected in the bone marrow, lymph nodes, thymus, and spleen. Although the three CD8+ CTL clones and two CTL lines tested required rhIL-2 for their engraftment, the four LAK cell populations also engrafted in the absence of rhIL-2. In contrast to CD8+ T cells, only low frequencies (<1%) of CD4+ cells could be detected in the blood of the SCID mouse. Engrafted human T cells recovered from the murine blood showed absent or diminished cytotoxicity in vitro against human target cells in five or six experiments, respectively. In addition, when the antitumor activity of engrafted CD8+ clones was investigated in vivo using a xenotransplantation model of human B-cell lymphoma in SCID mice, no significant prolongation of the mean survival time of six treated animals was observed compared with animals treated with rhIL-2 alone. Our results illustrate that although in vitro primed and cultured human CD8+ T cells engraft in SCID mice, their in vitro and in vivo function is impaired.

Animals↗

PubMed1998

A pancolitis resembling human ulcerative colitis (UC) is induced by CD4+ TCR alphabeta T cells of athymic origin in histocompatible severe combined immunodeficient (SCID) mice.

CD4+ TCRalphabeta+ T cells from the colonic lamina propria of athymic (nude) mice were adoptively transferred into histocompatible (SCID) mice homozygous for the autosomal recessive mutation scid (severe combined immunodeficiency). Transfer of these extrathymic CD4+ T cells into SCID mice induced a pancolitis in the adoptive host. The histopathology of this inflammatory response was restricted to the colon and closely resembled human UC. CD4+ T cells infiltrating the colonic lamina propria of diseased SCID mice displayed the surface phenotype of mucosa-seeking memory/effector cells, expressed interferon-gamma (IFN-gamma), and lysed targets in a Fas (CD95)/FasL-dependent pathway. Massive accumulation of oligoclonal CD4+ T cells of athymic origin with the phenotype of Th1 memory/effector T cells in the colonic lamina propria of a histocompatible, immunodeficient host elicits a pancolitis that morphologically mimics human UC.

Adoptive Transfer↗