Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0085110 (SCID)
 11,041 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Severe combined immunodeficiency (SCID) mice were engrafted with rheumatoid arthritis (RA) synovium and evaluated to determine whether RA synovial morphology and function were maintained in the RA-SCID grafts. The four major components of RA synovitis, inflammation, immune reactivity, angiogenesis, and synovial hyperplasia persisted in RA-SCID grafts for 12 weeks. Retention of chronic inflammatory infiltrates was demonstrated by histological evaluation and by immunohistology for CD3, CD20, and CD68. Staining for CD68 also revealed that the grafts had undergone reorganization of the tissue, possibly as a result of fibroblast hyperplasia. Immune and inflammatory components were confirmed by the detection of human immunoglobulins and human interleukin-6 in serum samples obtained from grafted animals. Human blood vessels were detected by dense expression of CD31. Small vessels persistently expressed the vitronectin receptor, alpha v beta 3, a marker of angiogenesis. All vessels expressed VAP-1, a marker of activated endothelial cells. Finally, the grafts retained the ability to support immigration by human leukocytes, as demonstrated by the functional capacity to recruit adoptively transferred 5- (and -6)-carboxyfluorescein diacetate succinimidyl ester-labeled T cells. T cells entering the RA-SCID grafts became activated and produced interferon-gamma, as detected by reverse transcriptase-polymerase chain reaction analysis. These studies demonstrate that the RA-SCID model maintains many of the phenotypic and functional features of the inflamed RA synovium.
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PMID:Inflammation, immune reactivity, and angiogenesis in a severe combined immunodeficiency model of rheumatoid arthritis. 1178 29

Previously, we showed that two temperature-sensitive mutants of murine cytomegalovirus (tsm5 and tsm30) expressed immediate-early (IE-1), early (E-1), and late (gB) phase genes in the tissues of immunocompetent Balb/c mice, yet failed to produce infectious progeny virus in any tissue at any time at 1-21 days post-infection. Mice inoculated intraperitoneally with tsm5 became latently infected, but this latent virus could not be reactivated as an infectious virus after immunosuppression, although all three transcripts were produced. Immunocompetent mice infected with tsm30 did not become latently infected. In the present study, immunodeficient SCID mice supported productive infection of both mutants, suggesting that low-level viral replication does occur in immunocompetent mice, but that it is limited by the host immune response. This is supported by the observation that immunocompetent mice were protected against virulent K181 challenge even after immunisation with as few as 40 pfu of mutant virus, whereas UV-inactivated mutant or K181 virus was not immunoprotective at doses of 40,000 pfu. Immunity induced by subcutaneous inoculation was also protective, whereas that induced by intragastric immunisation was not. Protection was lifelong (18 months). Although tsm5 induced high antibody titres, there was little evidence of an antibody response to tsm30. In contrast, a significant CD8(+) CTL response to the Balb/c immunodominant IE-1 nonapeptide (YPHFMPTNL) was elicited by both mutants, as determined by an interferon-gamma ELISPOT assay, although this response was lower than that induced by K181 infection. In addition, CTLs specific for m04 (YGPSLYRRF) and M84 (AYAGLFTPL) peptides could be detected at low frequency after K181, tsm5, and tsm30 immunisation. Such protective immunity did not prevent the challenge K181 virus from entering the latent state, but it appeared to reduce the frequency of reactivation.
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PMID:Immunisation of Balb/c mice with severely attenuated murine cytomegalovirus mutants induces protective cellular and humoral immunity. 1199 79

Histamine is produced by many cells expressing histidine decarboxylase (HDC), the enzyme responsible for the synthesis of histamine. Since melanoma cells and tissue contain relatively large amounts of histamine, the functional significance of histamine was examined using specific antihistamines in vitro and in vivo in the human melanoma cell line HT168 and severe combined immunodeficiency (SCID) mice. It was shown that the H2 receptor antagonist cimetidine when combined with N, N-diethyl-2-[4-(phenylmethyl)phenoxy]-ethanamine-HCl (DPPE), a tamoxifen derivate, inhibits the proliferation of HT168 cells. Furthermore, it is suggested that there is a factor(s) that interferes with the exponential growth of HT168 cells xenografted to immunodeficient mice, and cimetidine and DPPE together significantly influence this factor(s). This combination of antihistamines also increases the survival of human melanoma-grafted mice. These changes are accompanied by enhanced infiltration of interferon-gamma- producing mouse macrophages into the tumour tissue. These findings suggest that two different mechanisms are probably acting concordantly: direct inhibition of tumour cell proliferation by the H2 receptor antagonists, and activation of the local immune response characterized by interferon-gamma production. These findings may help to elucidate the possibility of a rationally designed antihistamine strategy in melanoma therapy.
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PMID:Cimetidine and a tamoxifen derivate reduce tumour formation in SCID mice xenotransplanted with a human melanoma cell line. 1214 Mar 79

To establish a more appropriate animal recipient for xenotransplantation, NOD/SCID/gamma(c)(null) mice double homozygous for the severe combined immunodeficiency (SCID) mutation and interleukin-2Rgamma (IL-2Rgamma) allelic mutation (gamma(c)(null)) were generated by 8 backcross matings of C57BL/6J-gamma(c)(null) mice and NOD/Shi-scid mice. When human CD34+ cells from umbilical cord blood were transplanted into this strain, the engraftment rate in the peripheral circulation, spleen, and bone marrow were significantly higher than that in NOD/Shi-scid mice treated with anti-asialo GM1 antibody or in the beta2-microglobulin-deficient NOD/LtSz-scid (NOD/SCID/beta2m(null)) mice, which were as completely defective in NK cell activity as NOD/SCID/gamma(c)(null) mice. The same high engraftment rate of human mature cells was observed in ascites when peripheral blood mononuclear cells were intraperitoneally transferred. In addition to the high engraftment rate, multilineage cell differentiation was also observed. Further, even 1 x 10(2) CD34+ cells could grow and differentiate in this strain. These results suggest that NOD/SCID/gamma(c)(null) mice were superior animal recipients for xenotransplantation and were especially valuable for human stem cell assay. To elucidate the mechanisms involved in the superior engraftment rate in NOD/SCID/gamma(c)(null) mice, cytokine production of spleen cells stimulated with Listeria monocytogenes antigens was compared among these 3 strains of mice. The interferon-gamma production from dendritic cells from the NOD/SCID/gamma(c)(null) mouse spleen was significantly suppressed in comparison with findings in 2 other strains of mice. It is suggested that multiple immunological dysfunctions, including cytokine production capability, in addition to functional incompetence of T, B, and NK cells, may lead to the high engraftment levels of xenograft in NOD/SCID/gamma(c)(null) mice.
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PMID:NOD/SCID/gamma(c)(null) mouse: an excellent recipient mouse model for engraftment of human cells. 1238 15

The expression of inducible nitric oxide synthase (iNOS) in two different murine wound models was investigated. Animals were subjected to either full-thickness linear skin incision with subcutaneous implantation of sterile polyvinyl alcohol sponges, or to 1.5 x 1.5-cm dorsal skin excision. Reverse transcriptase-polymerase chain reaction detected iNOS mRNA in all cell samples retrieved from the sponges. Immunoblotting of lysates of inflammatory cells harvested from the sponges failed to detect iNOS protein, and immunohistochemistry of the incisional wound was mildly positive. Inflammatory cells of excisional wounds stained strongly positive for iNOS. Cutaneous wounds were found to be colonized with Staphylococcus aureus. The detection of iNOS in cells from sponges inoculated in vivo with heat-killed bacteria and the reduction of immunohistochemical signal for iNOS in excisional wounds of animals treated with antibiotics support a role of bacteria in the induction of iNOS in wounds. The expression of iNOS in excisional wounds requires interferon-gamma and functional lymphocytes because interferon-gamma knockout and SCID-Beige mice exhibited attenuated iNOS staining in excisional wounds. The expression of iNOS in the inflammatory cells of murine wounds is a response to bacterial colonization and not part of the normal repair process elicited by sterile tissue injury.
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PMID:Bacterial colonization and the expression of inducible nitric oxide synthase in murine wounds. 1246 30

Alopecia areata is an autoimmune condition directed at hair follicles, which results in loss of hair. We have previously demonstrated that it is possible to transfer hair loss, along with the immunohistologic findings of alopecia areata, to human scalp grafts on Prkdc(scid) (SCID) mice by injection of autologous activated lesional T-cells. This study examines the cytokine profile of T-cells and follicular epithelium following transfer of hair loss. Two consistent findings significantly (P < 0.01) associated with hair loss were production of interferon-gamma-inducible protein-10 kDa (IP-10) by follicular epithelium (13/13), and production of INF-gamma by infiltrating T-cells (10/12). Noninjected control grafts regrew hair, and were generally negative for IP-10 (positive 2/9), and INF-gamma (positive 2/9), but expressed of IL-10 on the follicular epithelium (7/9). These data support an INF-gamma TH1 pathogenesis for hair loss in alopecia areata.
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PMID:Transfer of alopecia areata in the human scalp graft/Prkdc(scid) (SCID) mouse system is characterized by a TH1 response. 1270 4

Hair growth abnormalities in mice usually are accompanied by histologic abnormalities as well. Recently, however, we reported a mouse model in which an arrest of the hair cycle and diffuse shedding of the hair without pathologic features induced alopecia in interferon-gamma(-/-) (IFN-gamma(-/-)) C57BL/6 (B6) mice. Here, we explored the cellular origin of IFN-gamma. When bone marrow from IFN-gamma(-/-) B6 mice was transplanted into lethally irradiated IFN-gamma(+/+) B6 mice, the level of IFN-gamma mRNA expression in the skin or peripheral blood mononuclear cells (PBMCs) of recipient mouse was markedly reduced, suggesting that IFN-gamma is normally produced by bone marrow-derived cells. Although severe combined immunodeficiency (SCID) mice lack mature T cells and B cells, IFN-gamma-dependent hair regrowth was induced in SCID mice by depilation, which caused alopecia in IFN-gamma(-/-) B6 mice. Consistently, IFN-gamma mRNA expression in the skin or PBMC from SCID mice was comparable to that from their genetic counterpart (BALB/c mice), suggesting IFN-gamma production by non-T cells. RT-PCR analyses after separation of PBMC from SCID mice into eight fractions by a cell sorter revealed that Mac-1(+) cells were the major origin of IFN-gamma.
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PMID:Cellular origin of IFN-gamma essential for hair cycle in normal skin. 1285 56

We examined whether novel cytokines, interleukin (IL)-21 and IL-23, that were expressed in tumors could produce antitumor effects in the inoculated mice. Human pancreatic cancer AsPC-1 cells were retrovirally transduced with murine IL-21 or IL-23 (p19-linked p40) gene (AsPC-1/IL-21, AsPC-1/IL-23) and were injected into nude or severe combined immunodeficiency (SCID) mice. Although the proliferation in vitro of the transduced cells remained the same as that of parent cells, growth of AsPC-1/IL-21 and AsPC-1/IL-23 tumors developed in nude mice was retarded compared with that of parent tumors. Treatment of nude mice with anti-asialo GM(1) antibody temporally abrogated the growth retardation of AsPC-1/IL-21, but not AsPC-1/IL-23 tumors; however, the growth of AsPC-1/IL-21 tumors came to be retarded thereafter with the regeneration of natural killer (NK) cells. The growth of AsPC-1/IL-21 tumors developed in SCID mice was also retarded compared with parent tumors and the growth retardation was abrogated by treatment with anti-asialo GM(1) antibody. The growth of AsPC-1/IL-23 tumors in SCID mice was not different from that of parent tumors. Cytotoxic activity and secretion of interferon-gamma in response to AsPC-1 cells were induced in spleen cells of the mice bearing AsPC-1/IL-21 or AsPC-1/IL-23 tumors. When nude mice were injected with a mixed population of AsPC-1/IL-21 and AsPC-1/IL-23 cells, no synergistic effects were observed. These data collectively suggest that expression of IL-21 and IL-23 in tumors can produce NK cell-dependent and -independent antitumor effects in an alpha beta T cell-defective condition, respectively.
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PMID:Transduction of the IL-21 and IL-23 genes in human pancreatic carcinoma cells produces natural killer cell-dependent and -independent antitumor effects. 1450 30

Factor XIIIa-positive dendrocytes are abundant within the dermis and have been implicated in the pathogenesis of various disorders, including AIDS-related Kaposi's sarcoma. Purified cultures of factor XIIIa-positive normal dermal dendrocytes have not as yet been achieved. 12E2 is a cloned cell line derived from superficial murine dermis where factor XIIIa-positive dendrocytes are abundant. Subconfluent cultures of 12E2 demonstrate polydendritic cell contours with thin, elongated membranous projections. These cells express Factor XIIIa and VCAM-1 by immunohistochemistry and by Western blot analysis of 12E2 cell lysates. 12E2 cells also constitutively express the Langerhans-cell-related epitope DEC-205, detected by NLDC-145 antibody and the CD80 co-stimulatory molecule, as well as Ia antigen on exposure to interferon-gamma. Cells so treated exhibit significant ability to present alloantigens in vitro. 12E2 cells are shown to express mRNA for numerous cytokines, including interleukin (IL)-1alpha, IL-1beta, IL-5, IL-6, IL-7, tumor necrosis factor-alpha and granulocyte macrophage-colony stimulating factor, by reverse-transcriptase polymerase chain reaction followed by Southern blot hybridization. Microinjection of 12E2 cells, but not 3T3control fibroblasts, into footpads of syngeneic and SCID mice results in lesions that mimic the histology and immunohistochemistry of human Kaposi's sarcoma. In aggregate, these data indicate that 12E2 cells 1) share lineage characteristics with factor XIIIa-positive dermal dendrocytes, 2) produce mRNA for numerous cytokines and are cytokine responsive to interferon-gamma, and 3) behave in vivo in a manner that resembles Kaposi's sarcoma, a condition known to involve proliferation of human dermal dendrocytes.
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PMID:12E2: a cloned murine dermal cell with features of dermal dendrocytes and capacity to produce pathologic changes resembling early Kaposi's sarcoma. 1457 82

There is strong evidence indicating that alopecia areata is a tissue-specific, autoimmune disease. Hair loss is associated with a perifollicular lymphocytic infiltrate made up primarily of CD4+ cells, along with a CD8+ intrafollicular infiltrate. Evidence of immune activation includes expression of HLA-DR; HLA-A,B,C; and ICAM-1 on the follicular epithelium. It is likely that the follicular expression of HLA-DR and ICAM-1 is induced by interferon-gamma produced by T cells. Antibodies to follicular epithelium are often present, but their significance is not known. Lesional scalp from alopecia areata patients grafted onto nude mice regrows hair coincident with a loss of infiltrating lymphocytes from the graft. Hair loss can be transferred to human scalp explants on SCID mice by injection of lesional T cells. It is necessary to activate the T cells by culture with follicular autoantigens. Melanocyte-associated antigens are also capable of activating T cells to induce hair loss, suggesting that they are capable of functioning as autoantigens for alopecia areata. Parallel evidence in rodent models of spontaneous alopecia areata also strongly supports a role for T cells in the pathogenesis of this condition.
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PMID:Alopecia areata: autoimmunity--the evidence is compelling. 1458 66


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