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Biomedical subjects

P F Moore

Publications and source records attributed to P F Moore.

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

B-cell function in canine X-linked severe combined immunodeficiency.

Canine X-linked severe combined immunodeficiency (XSCID) is due to mutations in the common gamma (gammac) subunit of the IL-2, IL-4, IL-7, IL-9 and IL-15 receptors and has a similar clinical phenotype to human XSCID. We have previously shown that the block in T-cell development is more profound in XSCID dogs than in genetically engineered gamma c-deficient mice. In this study we evaluated the B-cell function in XSCID dogs. In contrast to the marked decrease in peripheral B-cells in gamma c-deficient mice, XSCID dogs have increased proportions and numbers of peripheral B-cells as observed in XSCID boys. Canine XSCID B-cells do not proliferate following stimulation with the T-cell-dependent B-cell mitogen, pokeweed mitogen (PWM); however, they proliferate normally in response to the T-cell-independent B-cell mitogen, formalin-fixed, heat-killed Staphylococcus aureus. Canine XSCID B-cells are capable of producing IgM but are incapable of normal class-switching to IgG antibody production as demonstrated by in vitro stimulation with PWM and immunization with the T-cell-dependent antigen, bacteriophage PhiX174. Similar results have been reported for XSCID boys. Thus, it appears that gamma c-dependent cytokines have differing roles in human and canine B-cell development than in the mouse making the XSCID dog a valuable model for studying the role of these cytokines in B-cell development and function.

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PubMed2000

Canine cutaneous and systemic histiocytosis: reactive histiocytosis of dermal dendritic cells.

Canine histiocytic proliferative disorders include reactive diseases such as cutaneous and systemic histiocytosis and neoplastic diseases such as cutaneous histiocytoma and localized and disseminated histiocytic sarcoma (malignant histiocytosis). Their etiology and pathogenesis are unknown. Canine cutaneous and systemic histiocytosis target the skin and subcutis and have similar clinical behavior. Systemic histiocytosis also affects other organ systems. Clinicopathologic and phenotypic features of canine cutaneous and systemic histiocytosis were examined in this study. Canine cutaneous (18 cases) and systemic (26 cases) histiocytosis were characterized by angiocentric, pleocellular accumulations consisting of CD1+, CD11c+, MHCII+, CD4+, and Thy-1+ (CD90) activated dermal dendritic antigen-presenting cells (APC) with admixed CD3+, CD8+, TCRalphabeta+ T lymphocytes, and neutrophils. Hence, canine cutaneous and systemic histiocytosis represent two clinical manifestations of a reactive proliferation of dermal dendritic cells. Cultures and special stains failed to identify infectious agents. Canine reactive histiocytoses respond to immunosuppressive therapy (cyclosporine A or leflunomide). Therefore, immune-dysregulatory mechanisms are likely to be involved. Spontaneous reactive histiocytoses are frequently seen in dogs, and they constitute an excellent model to study pathologic mechanisms involved in reactive proliferations of dermal dendritic APC.

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PubMed2000

Clinical, hematologic, and immunophenotypic characterization of canine large granular lymphocytosis.

Clinical, hematologic, and immunophenotypic data were studied in 25 dogs with large granular lymphocyte (LGL) lymphocytosis. Primarily large-breed dogs were affected, with an average age at initial diagnosis of 10 years (range 5-14 years). All dogs had persistent (>4 months) LGL lymphocytosis except for three that were euthanized with aggressive disease. Splenomegaly was reported in 12 of 20 dogs in which splenic size was evaluated. The clinical course was heterogeneous and dogs were divided into four groups based on similar clinical and hematologic findings: acute leukemia (3/25), persistent lymphocytosis with anemia (12/25), persistent lymphocytosis without anemia (8/25), and reactive lymphocytosis (2/25). Immunophenotypes varied within groups but were homogeneous among cells from the same patient except in the two dogs classified as reactive LGL lymphocytosis. Analysis of T-cell receptor (TCR) usage identified three main LGL lineages. TCRalphabeta was expressed in 15/25 (60%) cases. TCRgammadelta was expressed in 8/25 (32%) cases, and 2/25 (8%) cases were CD3-, compatible with NK cells. beta2 integrin expression was distinctive. CD11a was consistently expressed, while CD11b was absent. CD11c was expressed only weakly in 16/25 (64%) cases. The leukointegrin alphadbeta2 was highly prevalent on all LGL lineages, being expressed in 23/25 (92%) cases. Prominent involvement of the spleen, relative sparing of bone marrow, an unexpectedly large proportion of gammadelta T-cell LGLs, and the distinctive beta2 integrin expression pattern on diverse lineages of LGLs suggest the disease arises from unique populations of lymphocytes that preferentially localize in the splenic red pulp.

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PubMed1999

Investigation of recombinant human insulin-like growth factor type I in thymus regeneration in the acute stage of experimental FIV infection in juvenile cats.

Thymus involvement and the development of thymic lesions in HIV-1 infection is hypothesized to suppress thymus function and limit T cell maturation and replenishment of the peripheral lymphoid pool. Therapeutic modulation to protect or enhance thymus function may therefore ameliorate peripheral lymphocytopenia and retard disease progression. Thymotrophic agents, such as insulin-like growth factor type I (IGF-I), may therefore represent adjunctive but important methods of treatment to protect or promote thymus function. The assessment of rhIGF-I in lentiviral infection and its impact on the thymus was performed using the feline immunodeficiency virus (FIV) model. Regeneration of the thymus in juvenile cats and amelioration of the thymic lesion after FIV infection was assessed by multiple measurements including thymic weight, stereologic analysis of the thymus cortex and medulla, histologic and immunohistologic analysis, quantitation of thymocyte and peripheral lymphocyte subsets, and quantitative competitive RT-PCR. Evidence of thymic cortical regeneration was observed in FIV-inoculated cats after 12 and 20 weeks of rhIGF-I treatment. Inflammation in the thymus was reduced during this period of treatment in this group of rhIGF-I/FIV-inoculated cats as evidenced by the reduced numbers of B cells detected. Viral replication rates in peripheral lymph nodes were not altered by rhIGF-I treatment and were decreased by 1 log in the thymus after 20 weeks of treatment. Peripheral blood CD4+ T cell counts also increased after 14 weeks of treatment. This suggests that rhIGF-I treatment can enhance thymus function and replenishment of the peripheral T cell pool.

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PubMed1999

Canine X-linked severe combined immunodeficiency.

Canine X-linked severe combined immunodeficiency (XSCID) is due to mutations in the common gamma (gamma c) subunit of the IL-2, IL-4, IL-7, IL-9 and IL-15 receptors. The most striking clinical feature is a failure to thrive or 'stunted' growth. Recurrent or chronic infections begin at the time of decline of maternal antibody, usually between six and eight weeks of age. Affected dogs rarely survive past three to four months of age. The major pathologic feature of canine XSCID is a small, dysplastic thymus. Grossly identifiable lymph nodes, tonsils, and Peyer's patches are absent in XSCID dogs. During the neonatal period, XSCID dogs have few, if any, peripheral T cells and increased number of peripheral B cells. Some XSCID dogs do develop phenotypically mature, nonfunctional T cells with age, however, the absolute number of peripheral T cells remain significantly decreased compared to age-matched normal dogs. An interesting finding is that as soon as T cells begin to appear in XSCID dogs they rapidly switch from a CD45RA+ (naive) phenotype to a CD45RA- (activated or memory phenotype). One of the characteristic findings in XSCID dogs is an absent or markedly depressed blastogenic response of T cells in response to stimulation through the T cell receptor and when the necessary second messengers for cellular proliferation are directly provided that by-pass signals delivered through ligand-receptor interaction. The proliferative defect is due to the inability of T cells to express a functional IL-2 receptor. Canine XSCID B cells do not proliferate following stimulation with T cell-dependent B cell mitogens, however, they proliferate normally in response to T cell-independent B cell mitogens. Canine XSCID B cells are capable of producing IgM but are incapable of class-switching to IgG antibody production following immunization with the T cell-dependent neoantigen, bacteriophage phiX174. The number of thymocytes in the XSCID thymus is approximately 0.3% of the thymocytes present in the thymus of age-matched normal dogs. The proportion of CD4-CD8- thymocytes in XSCID dogs is increased 3.5-fold and the CD4+CD8+ population is decreased 2.3-fold. These findings demonstrate that (1) a functional gamma c is required for normal B and T cell function, (2) early T cell development is highly dependent upon a functional gamma c, and (3) B cell development can occur through a gamma c-independent pathway.

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PubMed1999

Bone marrow transplantation for canine X-linked severe combined immunodeficiency.

Canine X-linked severe combined immunodeficiency (XSCID) is due to mutations in the common gamma chain which is a subunit of the receptors of IL-2, IL-4, IL-7, IL-9 and IL-15. Bone marrow transplantation (BMT) of human XSCID patients without pretransplant conditioning (cytoablation) results in engraftment of donor T-cells and reconstitution of T-cell function but engraftment of few, if any, donor B cells with resultant poor reconstitution of humoral immune function. In this study, we show that XSCID dogs can be transplanted with allogeneic bone marrow cells resulting in engraftment of both donor B and T cells and reconstitution of full systemic immune function including normal humoral immune function without the need for cytoablation.

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PubMed1999

An immunophenotypic study of canine leukemias and preliminary assessment of clonality by polymerase chain reaction.

There is a relative lack of information in the veterinary literature regarding the immunophenotypes present in canine leukemias. Utilizing a panel of thirty monoclonal antibodies, canine leukemias were assessed by flow cytometry alone or by flow cytometry in combination with immunocytochemical staining of smears. Canine chronic lymphocytic leukemia (CLL) occurred in older dogs (mean age 9.75 years; range 1.5-15 years; n = 73 cases). Blood lymphocyte counts ranged from 15,000 to 1,600,000/microl. Surprisingly, 73% of CLL cases involved proliferation of T lymphocytes (CD3+), and 54% of CLL cases had large granular lymphocyte (LGL) morphology. LGL CLL's were almost exclusively proliferation's of T cells that expressed CD8 and the leukointegrin alphaDbeta2 and more frequently expressed T cell receptor (TCR) alphabeta (69%) than TCRgammadelta (31%). The non-LGL T cell CLL cases (19% of CLL) involved proliferation of TCRalphabeta T cells in which no consistent pattern of CD4 or CD8 expression was found. B cell CLL, based on expression of CD2 or CD79a, comprised 26% of canine CLL cases. These results are in marked contrast to people where greater than 95% of CLL cases involve proliferation of B lymphocytes. Thirty eight (38) acute leukemias were also immunophenotyped. The majority (55%) of these leukemias had a phenotype most consistent with a myeloid origin. Acute LGL leukemias were also observed (7/38), although less commonly than the CLL counterpart. CD34 expression was common in acute, non-LGL leukemias of dogs, both myeloid and lymphoid. In some circumstances, it can be difficult to differentiate a reactive (polyclonal) lymphoid proliferation from a neoplastic (monoclonal) one. Therefore, as an adjunct to phenotypic studies, we have developed a polymerase chain reaction (PCR) based test for assessment of clonality in T cell proliferations. The test amplifies the junction of the variable gamma (Vgamma) and joining gamma (Jgamma) gene segments region of the TCR gamma genes. Preliminary data indicates that our test is effective and is capable of differentiating a neoplastic from a reactive lymphoproliferative process.

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PubMed1999

The use of an anti-TCRalphabeta monoclonal antibody to control host-versus-graft reactions in canine marrow allograft recipients conditioned with low dose total body irradiation.

BACKGROUND: A limitation in the application of marrow transplantation has been complications related to the conditioning regimens that have been intensified to the point where organ toxicities have been common, resulting in morbidity and mortality. METHODS: A conditioning regimen consisting of low-dose total body irradiation (TBI*) was used to test whether postgrafting therapy with a monoclonal antibody (mAb) against the T cell receptor (TCR)alphabeta facilitated sustained engraftment of marrow from dog leukocyte antigen (DLA)-identical canine littermates. The anti-TCRalphabeta mAb 15.9D5 was selected for in vivo studies because it induced hyporesponsiveness to allogeneic stimulator cells in mixed leukocyte culture and was not mitogenic in vitro. RESULTS: When recipients of genotypically DLA-identical marrow were conditioned by the barely "lethal" dose of 450 cGy TBI alone, almost 60% of grafts failed (n=39). The remainder engrafted, either in the form of stable mixed donor/host or all donor hematopoietic chimerism. In contrast to results in controls, 5 of 6 dogs that were given, in addition, a loading dose of mAb 15.9D5 of 1 mg/kg on day -1, 450 cGy TBI on day 0, followed by mAb at 0.3 mg/kg/day until day +7, showed sustained engraftment (P=.058). To accomplish a comparable rate of engraftment in the absence of anti-TCRalphabeta antibody, 920 cGy TBI were needed for pretransplant conditioning. CONCLUSIONS: Results strongly suggested that in vivo administration of a mAb against TCRalphabeta prevented rejection of allogeneic marrow grafts in the setting of conditioning with a relatively nontoxic but otherwise suboptimal dose of 450 cGy TBI. In vivo administration of m Ab 15.9D5 was well tolerated without any noticeable side effects. The exact mechanism by which the mAb works in vivo is as yet poorly understood, but it does not involve CD3/TCR complex modulation or elimination of T cells from the circulation.

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PubMed1999

The distribution of lymphocytes expressing alphabeta and gammadelta T-cell receptors, and the expression of mucosal addressin cell adhesion molecule-1 in the canine intestine.

The present study defined the distribution of alphabeta and gammadelta T-cell subsets, and the expression of mucosal addressin cell adhesion molecule-1 (MAdCAM-1) in the intestinal tract of an outbred population of dogs with no evidence of gastrointestinal disease. A panel of monoclonal antibodies reactive with the canine alphabeta and gammadelta T-cell receptors (TCRs) and human MAdCAM-1 was used in a series of immunoperoxidase or immunofluorescence studies. alphabeta T cells were predominant within the villous lamina propria with a significantly decreasing linear trend from upper villus to crypt (P<0.0001). A proportion of intraepithelial lymphocytes (IELs) also expressed the alphabeta T-cell receptor, with significantly greater numbers in villous than in crypt epithelium (P<0.0001). However, there were no significant differences in the numbers of either lamina propria or epithelial alphabeta T cells between different intestinal regions. gammadelta T cells were rare in the lamina propria, but a prominent gammadelta IEL population was present and shown by double-colour immunofluorescence studies to be principally of the CD4(&)minus;CD8alpha(&)minus; phenotype. MAdCAM-1 was expressed by endothelial cells in the mucosa, sub-mucosa and muscularis layers of all levels of the intestinal tract. In the mucosa, significantly more MAdCAM-1 positive endothelium was present in regions of crypt than villous lamina propria (P<0.0001), but there were no significant differences between expression in different intestinal regions. The quantitative and qualitative data will enable comparisons of these parameters to be made with those in dogs suffering from inflammatory bowel diseases.

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PubMed1999

Toward a canine model of atopic dermatitis: amplification of cytokine-gene transcripts in the skin of atopic dogs.

The objectives of the present study were to characterize and compare the repertoire of cytokine-genes transcribed in skin homogenates obtained from normal dogs and dogs with atopic dermatitis (AD) using a reverse-transcriptase polymerase chain reaction and canine-specific cytokine-gene primers. Whereas IL-4 and IL-5 cytokine-gene transcripts were detected more commonly in atopic skin biopsy homogenates, IL-2 mRNA was amplified more often from normal control specimens. IFN-gamma mRNA was detected in 5/29 atopic specimens, 4 of them obtained from the only dog with chronic skin lesions. One-fourth of atopic samples exhibited clear type-2 cytokine profiles; the remainder did not demonstrate polarized repertoires. Conversely, type-1 cytokine profiles were characterized in one-fourth of normal control specimens. The present study establishes, for the first time, the transcription of type-2 cytokine-genes in the skin of dogs with AD. Future experiments investigating the cellular origin and dynamics of allergic cytokine-gene transcription are needed to confirm whether or not canine AD could be considered an immunological model for a human disease.

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PubMed1999

Compensation for decreased expression of B7 molecules on Leishmania infantum-infected canine macrophages results in restoration of parasite-specific T-cell proliferation and gamma interferon production.

Infection of humans and dogs by Leishmania infantum may result in visceral leishmaniasis, which is characterized by impaired T-cell-mediated immune responses to parasite antigens. Dogs are natural hosts of Leishmania parasites and play an important role in the transmission of the parasites to humans. In an effort to characterize the immune response in dogs infected with this intracellular pathogen, we examined how infection with L. infantum affects canine macrophages and the consequences for T-cell activation in vitro. We showed that the proliferation of T-cell lines to cognate antigen decreases to background levels when infected autologous monocyte-derived macrophages are used as antigen-presenting cells (APC). The observed reduction of antigen-specific T-cell proliferation was shown to be dependent on the parasite load and to require cell-to-cell interaction of T cells with the infected APC. In addition, we observed a decreased expression of costimulatory B7 molecules on infected monocyte-derived macrophages. The expression of other surface molecules involved in T-cell activation, such as major histocompatibility complex class I and class II, on these cells did not change upon infection, whereas the expression of intracellular adhesion molecule 1 was marginally increased. Compensation for the decreased expression of B7 molecules by the addition of B7-transfected cells resulted in the restoration of cell proliferation and gamma interferon (IFN-gamma) production by a Leishmania-specific T-cell line. These results showed that for the activation of parasite-specific canine T cells producing IFN-gamma, which are most likely involved in protective immunity, sufficient expression of B7 molecules on infected macrophages is required. Provision of costimulatory molecules may be an approach for immunotherapy of leishmaniaisis as well as for vaccine development.

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PubMed1998

Canine T cells transduced with a herpes simplex virus thymidine kinase gene: a model to study effects on engraftment and control of graft-versus-host disease.

BACKGROUND: Alloreactive donor T cells in marrow grafts mediate graft-versus-host disease (GVHD), but T-cell depletion has resulted in increased graft failure. Add-back of gene-modified alloreactive donor T cells could prevent graft rejection. After engraftment, in vivo depletion of those modified T cells with ganciclovir may control GVHD. METHODS: Canine recipient-specific donor cytotoxic T lymphocytes (CTL) were retrovirally transduced with the herpes simplex virus thymidine kinase gene. RESULTS: Gibbon ape leukemia virus-pseudotyped vector yielded primary CTL transduction efficiency of 22.9+/-9.9%. After selection and expansion, 96.7+/-0.8% of CTL expressed retrovirally transferred genes. Recipient-specific cytotoxic activity was maintained with 84.3% specific lysis. After ganciclovir treatment, herpes simplex virus thymidine kinase-transduced CTL proliferation was reduced 98.7+/-0.2% compared with controls. CONCLUSIONS: We have demonstrated efficient ex vivo transduction, expansion, maintenance of alloreactivity, and ganciclovir-mediated ablation of canine CTL, which will permit in vivo studies in the dog, a well-established model for GVHD and engraftment.

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PubMed1998

Analysis of the immunological cross reactivities of 213 well characterized monoclonal antibodies with specificities against various leucocyte surface antigens of human and 11 animal species.

213 Monoclonal antibodies (mAbs) raised against leucocyte surface antigens from human and 11 animal species were analyzed for reactivities against leucocytes from human and 15 different animal species. We found 77 mAbs (36%) to cross-react. Altogether, 217 cross reactions were registered out of 3195 possible combinations (7%). Most of the cross reacting mAbs had integrin or MHC class II specificities. This study defined cross reactions on the following markers: CD1a, 1c, 2, 4, 5, 8, 9, 11a, 11b, 14, 18, 20, 21, 23, 29, 31, 41, 43, 44, 45, 45R, 46, 49, 61, 62L, TCR gamma/delta, BCR, Thy-1, MHC class I and MHC class II, Swine-WC7 and Cattle-WC1. In order to characterize the molecular weight (MW) of the corresponding cross reacting antigens, selected mAbs were used to immunoprecipitate the antigens. The MW's of the analyzed precipitated antigens were in good agreement with the MWs of the homologous antigens. The followed strategy was found to be efficient and economical in defining new leucocyte antigen reactive mAbs.

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PubMed1998

Report of the Second Equine Leucocyte Antigen Workshop, Squaw valley, California, July 1995.

The final assignment of antibody clusters for leucocyte antigens and immunoglobulins, as described in detail in Sections 3 and 4, is summarized in Table 4. Together with other mAbs developed outside of ELAW II (Table 9) this pool of reagents represent a powerful array of tools for the study of equine immunity. The Second Equine Leucocyte Antigen Workshop made considerable advances in pursuing the objectives of establishing the specificities of mAbs and achieving consensus on the nomenclature for equine leucocyte and immunoglobulin molecules. Of equal importance, several productive collaborations were fostered among the participating laboratories and observers. Overall, enormous advances have been made in the past decade since mAbs specific for equine leucocyte antigens and immunoglobulins were first reported. There remains enormous scope and need for further studies of equine leucocyte antigens and immunoglobulins, both for the purposes of comparative immunology and for the good of the horse. In the future novel techniques will be required to develop reagents for specific target antigens such as the orthologues of the CD25 or CD45 isoforms. In studies of equine immunoglobulins the functional role of the IgG isotypes must be better established, reagents for IgE must be developed, and cloning of the immunoglobulin heavy chain genes will be essential if the complexities of the IgG sub-isotypes are to be elucidated. The tasks still facing the currently small group of equine immunologists throughout the world remain formidable, and will only be tackled successfully in a spirit of collaboration.

Animals↗
PubMed1998

The expression and differentiation pattern of cell antigens and adhesion molecules on the nonadherent cell population in canine long-term marrow culture: a biphasic development of myeloid and lymphoid cells.

During maturation of normal hematopoietic progenitors, there appears to be differentiation-dependent expression of adhesion receptors, which may contribute to the homing and lodging of stem progenitor cells into the marrow and for the eventual release of mature effector cells from the marrow cavity. Using a model of long-term marrow culture, we studied the expression pattern of different lineage cell antigens and cell adhesion molecules on the nonadherent cells in canine long-term marrow culture. CD4+ cells became a major proportion of both the small and large cell subsets by day 8 of culture. Small CD4+ cells, the majority of which are negative for other T-cell antigens during the first 2 weeks of culture, express low levels of CD4 (CD4lo) and coexpress granulocytic and/or monocytic markers. These CD4lo cells have progenitor potential as measured by the long-term culture-initiating cell assay and differentiate into myeloid (first wave) and lymphoid (second wave) cells. The T cells, which appear in 2-week-old long-term marrow culture, respond to Con A but not to alloantigen. At the same time, most of the large cells are CD14+, CD11b+, DLA-DR+ and CD4lo+, while granulocytes are not observed. This phenotypic pattern closely resembles that found on myelomonocytic cells developing from fetal thymic and fetal liver CD34+ precursors in a model of human fetal thymic organ culture. The cell adhesion molecules--CD44, CD18, L-selectin, CD11a-c as well as VLAalpha4, dramatically increase from the first week of long-term marrow culture, while ICAM-1 and a new beta2 cell adhesion molecule, alpha dbeta2, increased slightly from the third week on. In the large ("monocytic") cell population, alpha dbeta2 was exclusively expressed by CD4+ cells. The differentiation pattern of T-cell antigens and adhesion molecules seen in the canine long-term marrow culture appear to mimic those required for developmental interactions between leukocytes and endothelial cells; that is, an early expression of L-selectin and CD44, followed by the integrins, and later on by ICAM-1 and alpha dbeta2. Our data support the view that in a model of canine long-term marrow culture hematopoietic precursors retain their intrinsic developmental potential.

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PubMed1997

Full immunologic reconstitution following nonconditioned bone marrow transplantation for canine X-linked severe combined immunodeficiency.

Bone marrow transplantation in human X-linked severe combined immunodeficiency (XSCID) without pretransplant conditioning results in engraftment of donor T cells and reconstitution of T-cell function but engraftment of few, if any, donor B cells and poor reconstitution of humoral immune function. Since bone marrow transplantation remains the most effective treatment of XSCID patients, better strategies are necessary to achieve optimum long-term results. Canine XSCID, like human XSCID, is due to mutations in the common gamma chain (gamma c) gene and has clinical and immunologic features identical to those of human XSCID, making it a true homolog of the human disease. We have successfully performed bone marrow transplantation in three XSCID dogs without pretransplant conditioning, using untreated bone marrow cells from mixed lymphocyte culture-nonreactive normal littermates. Unlike the experience in human XSCID patients, all three dogs engrafted both donor B and T cells and attained full reconstitution of immunologic function. Normal percentages of T cells and T-cell mitogenic responses were attained by 3 months posttransplant. CD3+ T cells after transplantation expressed the CD45RA isoform indicating that the cells were recent thymic emigrants derived from immature progenitors. Serum IgG levels were within normal range by 5 months posttransplant. Immunization with the T-dependent antigen, bacteriophage phiX174, demonstrated normal antibody titers, immunologic memory, and class-switching. Polymerase chain reaction (PCR) analysis of the gamma c locus showed that 100% of circulating T cells and 30% to 50% of circulating B cells were donor-derived. None of the dogs developed clinically evident graft-versus-host disease (GVHD). Thus, canine XSCID provides a model to determine the optimal conditions for bone marrow transplantation in human patients, and to develop and test strategies for somatic gene therapy.

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