Human squamous cell carcinomas of the head and neck chemoattract immune suppressive CD34(+) progenitor cells

CD34(+) progenitor cells have previously been shown to be mobilized in patients with squamous cell carcinoma of the head and neck (HNSCC). The present study showed that these CD34(+) cells inhibit the capacity of intratumoral lymphoid cells to become activated in response to stimulation through the TCR/CD3 complex. The mechanisms that could lead to the accumulation of CD34(+) cells within the tumor tissue were assessed. This was accomplished through in vitro studies that determined if HNSCC produce soluble factors that chemoattract CD34(+) cells. The migration of cord blood CD34(+) cells, which were used as a readily available source of progenitor cells, was stimulated by products derived from HNSCC explants and primary HNSCC cultures. This stimulated migration was due to chemotaxis because it was dependent on an increasing gradient of HNSCC-derived products. CD34(+) cells that were isolated from the peripheral blood of HNSCC patients were similarly chemoattracted to the HNSCC-derived products. The majority of the chemotactic activity produced by HNSCC could be attributed to vascular endothelial cell growth factor (VEGF). These studies indicate that HNSCC can chemoattract immune inhibitory CD34(+) progenitor cells through their production of VEGF.     

Myeloid progenitor cells mediate immune suppression in patients with head and neck cancers.

Patients with squamous cell carcinomas of the head and neck (HNSCC) have profound defects in their immune defenses. We have shown that among the mechanisms that contribute to this immune dysfunction are immune inhibitory CD34+ progenitor cells, whose levels become elevated in the peripheral blood and within the tumor tissue. One goal of our studies is to overcome the immune inhibitory activities of tumor-induced CD34+ progenitor cells by stimulating their differentiation into cells, such as dendritic or monocytic cells, that can stimulate immune reactivity to autologous cancer. Results of in vitro analyses with CD34+ suppressor cells of HNSCC patients and of in vivo studies in animal tumor models have shown the capacity of tumor-induced CD34+ cells to differentiate into cells that phenotypically resemble monocytic or dendritic cells. Whether these cells can differentiate into dendritic cells in HNSCC patients is currently being tested. Less clear is whether the pathway by which the tumor-induced CD34+ cells differentiate will result in cells having the full capacity to function as potent stimulators of immune reactivity to autologous tumor.     

Cultures derived from peripheral blood CD34+ progenitor cells of head and neck cancer patients and from cord blood are functionally different

Patients with head and neck squamous cell carcinoma (HNSCC) have profound immune defects mediated, in part, by an increased number of immune suppressive CD34⁺ progenitor cells in their peripheral blood and tumor. One means of overcoming this immune suppression is to stimulate the CD34⁺ cells to differentiate into more mature, nonsuppressive progeny such as dendritic cells or monocytes. This study determined that CD34⁺ cells from the peripheral blood of HNSCC patients have the same potential to differentiate into dendritic cells as do human umbilical cord blood CD34⁺ cells following 12–16 days of culture with a cytokine cocktail. When compared functionally, the cultures that developed from CD34⁺ cells of cord blood were able to induce an allostimulatory response in naive T-cells, while the cultures that developed from patient CD34⁺ cells lacked allostimulatory ability. Both cultures expressed class II MHC (HLA-DR), but the proportion of cells expressing the costimulatory molecules CD80 and CD86 was significantly less in cultures that developed from HNSCC-patient CD34⁺ cells. Therefore, although the CD34⁺ cells from the peripheral blood of HNSCC patients can differentiate into dendritic cells, their allostimulatory capabilities are impaired, raising the question of their potential effectiveness in stimulating antitumor immune responses.     

In vitro expanded cells contributing to rapid severe combined immunodeficient repopulation activity are CD34+38-33+90+45RA-

Expansion of hematopoietic stem cells could be used clinically to shorten the prolonged aplastic phase after umbilical cord blood (UCB) transplantation. In this report, we investigated rapid severe combined immunodeficient (SCID) repopulating activity (rSRA) 2 weeks after transplantation of CD34(+) UCB cells cultured with serum on MS5 stromal cells and in serum- and stroma-free cultures. Various subpopulations obtained after culture were studied for rSRA. CD34(+) expansion cultures resulted in vast expansion of CD45(+) and CD34(+) cells. Independent of the culture method, only the CD34(+)33(+)38(-) fraction of the cultured cells contained rSRA. Subsequently, we subfractionated the CD34(+)38(-) fraction using stem cell markers CD45RA and CD90. In vitro differentiation cultures showed CD34(+) expansion in both CD45RA(-) and CD90(+) cultures, whereas little increase in CD34(+) cells was observed in both CD45RA(+) and CD90(-) cultures. By four-color flow cytometry, we could demonstrate that CD34(+)38(-)45RA(-) and CD34(+)38(-)90(+) cell populations were largely overlapping. Both populations were able to reconstitute SCID/nonobese diabetic mice at 2 weeks, indicating that these cells contained rSRA activity. In contrast, CD34(+)38(-)45RA(+) or CD34(+)38(-)90(-) cells contributed only marginally to rSRA. Similar results were obtained when cells were injected intrafemorally, suggesting that the lack of reconstitution was not due to homing defects. In conclusion, we show that after in vitro expansion, rSRA is mediated by CD34(+)38(-)90(+)45RA(-) cells. All other cell fractions have limited reconstitutive potential, mainly because the cells have lost stem cell activity rather than because of homing defects. These findings can be used clinically to assess the rSRA of cultured stem cells.     

Impaired NK cell differentiation of blood-derived CD34+ progenitors from patients with myeloid metaplasia with myelofibrosis

Cultured blood CD34(+) progenitors from patients with myeloid metaplasia with myelofibrosis (MMM) failed to differentiate into natural killer (NK) cells with recombinant interleukin (IL)-15. No NK cells either could be induced in coculture with IL-15-expressing fibroblasts from MMM patients' spleens. The impaired NK differentiation could be circumvented by using normal blood CD34(+) cells in the coculture. In this case, cell-to-cell contact and IL-15 interaction were crucial for NK cell differentiation. Pretreatment of normal CD34(+) progenitors with anti-IL-15 monoclonal antibody markedly reduced NK cell production while MMM fibroblast pretreatment did not. Both normal and MMM progenitors constitutively expressed IL-15. Analysis of endogenous IL-15 signaling pathway revealed a constitutive gammac/Jak3 association and STAT3 activation in the two types of progenitors. Anti-IL-15 monoclonal antibody treatment caused a downregulation of IL-15 signaling in normal but not MMM blood cells. The impaired NK differentiation in MMM may thus arise from a deregulated control of an endogenous IL-15 involved in hematopoietic progenitors' lymphoid differentiation.     

Altered immunoregulatory profile during anti-tumour necrosis factor treatment of patients with inflammatory bowel disease

Inflammatory bowel disease (IBD) can be treated effectively by anti-tumour necrosis factor (TNF) therapy. We set out to investigate the unclear immunoregulatory mechanisms of the treatment. Thirty-four patients with IBD treated with anti-TNF were included. Lymphocytes from peripheral blood and intestinal biopsies were analysed by flow cytometry. Regulation of antigen-stimulated proliferation was analysed by blocking of interleukin (IL)-10, transforming growth factor (TGF)-β or depletion of CD25(+) cells in peripheral blood mononuclear cell cultures. No changes in CD4(+)CD25(+), CD25(+)TNF-RII(+) or CD4(+)CD25(+) forkhead box protein 3 (FoxP3(+)) T cells could be observed in peripheral blood after, in comparison to before, 6 weeks of treatment. The suppressive ability of CD4(+)CD25(+) cells did not change. There was an initial decrease of CD4(+)CD25(+) cells in intestinal mucosa after 2 weeks of treatment, followed by an increase of these cells from weeks 2 to 6 of treatment (P < 0·05). This was accompanied by an increased percentage of CD69(+) cells among these cells after 6 weeks of treatment compared to before treatment (P < 0·01). There was also an increase of mucosal T helper type1 cells from weeks 2 to 6 (P < 0·05). In addition, CD25(+)TNF-RII(+) cells in the mucosa were decreased after 6 weeks of treatment compared to before treatment (P < 0·05). Before treatment, peripheral blood mononuclear cell baseline proliferation was increased when IL-10 was blocked (P < 0·01), but not after. In CD25(+) cell-depleted cultures proliferation increased after treatment (P < 0·05). Our data indicate that anti-TNF treatment leads to an induction of effector T cells. Anti-TNF therapy has no significant impact on regulatory T cells in IBD, although the composition of regulatory T cell subsets may change during treatment.     

Generation of natural killer cells from serum-free, expanded human umbilical cord blood CD34+ cells

Natural killer (NK) cells are important effectors of the innate immune system, which exhibits cytolytic activity against infectious agents and tumor cells. NK cells are derived from CD34(+) hematopoietic stem cells (HSCs). Human umbilical cord blood (UCB) has been recognized as a rich source of HSCs. Previously, we have reported an optimized serum-free medium for ex vivo expansion of CD34(+) cells from UCB. In this study, the serum-free, expanded CD34(+) cells were tested to differentiate into NK cells and their induction kinetics. After 5 weeks of induction, the induced NK cells were characterized by analysis of surface antigens, IFN-gamma secretion, and cytotoxicity against K562 cells. The results indicated that NK cells derived from the serum-free, expanded CD34(+) cells exhibited both characteristics and functions of NK cells. Furthermore, the serum-free, expanded CD34(+) cells showed a significantly higher NK cell differentiation potential than freshly isolated CD34(+) cells. NK cells induced from serum-free, expanded CD34(+) cells showed a higher concentration of IFN-gamma secretion and ability of cytotoxicity than those from freshly isolated CD34(+) cells. Therefore, ex vivo-expanded CD34(+) cells in optimized serum-free medium could differentiate into NK cells and provided a promising cell source for immunotherapeutic approaches.     

Cycling CD34 expression in subpopulations of head and neck squamous cell carcinoma cell lines is involved in radioresistance and change in cytokeratin expression profile

The expression of the hair follicle stem cell marker CD34 was analyzed in five different head and neck squamous cell carcinoma (HNSCC) cell lines with different antibodies. All HNSCC cell lines expressed CD34 on their cell surface. After cell cycle synchronization via serum starvation, we observed cyclic CD34 expression in HNSCC cells dependent on cell cycle progression via immunofluorescent staining and flow cytometric analysis. Investigation of the CD34(+) and CD34(?) HNSCC populations revealed most of the cells in S-phase and G2/M-Phase in CD34(+) cells in contrast to CD34(?) cells. Knockdown of CD34 in HNSCC cells led to diminished clonal expansion in a colony forming assay after subjecting the cells to ionizing radiation. Furthermore, knockdown of CD34 after cell cycle synchronization induced high CK1, CK4, and CK5 gene expression and downregulation of CK10 gene expression as shown by Taqman^® quantitative PCR analysis. The expression levels of CK1 and CK10 were verified via western blot analysis. In summary, our study shows that CD34 plays a role during cell cycle progression of head and neck squamous cell carcinoma and additionally is involved in irradiation resistance and differentiation of malignant oral keratinocytes.     

Dendritic cell differentiation pathways of CD34+ cells from the peripheral blood of head and neck cancer patients.

Patients with head and neck squamous cell carcinoma (HNSCC) have increased levels of immune-suppressive peripheral blood CD34+ cells. This study showed that the peripheral blood CD34+ cells of HNSCC patients are capable of differentiating into dendritic cells. Because CD34+ cells can differentiate through several pathways into dendritic cell subpopulations, the intermediate cells through which the blood CD34+ cells of HNSCC patients differentiate were identified. After 6-7 days of culturing the CD34+ cells of HNSCC patients with granulocyte-macrophage colony-stimulating factor, stem cell factor, and tumor necrosis factor at, there appeared CD14+CD1a+ and a lesser proportion of CD14(-)CD1a+ cells resembling the precursor cells of the bipotential and committed dendritic cell differentiation pathways that have been described for cord blood CD34+ cells. To functionally analyze whether these populations were in fact precursor cells, they were isolated and cultured for an additional 10-12 days. Each of these populations was shown to function as precursor cells because they were able to develop into cells that resembled dendritic cells, although a higher proportion developed from the CD14-CD1a+ cells. In contrast, expression of the dendritic activation/maturation marker CD83 was highest on the cells that developed from CD14+CD1a+ cells. Thus, the CD34+ cells whose levels are increased in HNSCC patients can develop into both committed and bipotential dendritic precursor cells, which can subsequently give rise to dendritic cells.     

Cord blood-hematopoietic stem cell expansion in 3D fibrin scaffolds with stromal support

Expansion of multipotent, undifferentiated and proliferating cord blood (CB)-hematopoietic stem cells (HSC) in?vitro is limited and insufficient. Bone marrow (BM) engineering in?vitro allows mimicking the main components of the hematopoietic niche compared to conventional expansion strategies. In this study, four different 3D biomaterial scaffolds (PCL, PLGA, fibrin and collagen) were tested for freshly isolated cord blood (CB)-CD34(+) cell expansion in presence of (i) efficient exogenous cytokine supplementation and (ii) umbilical cord (UC)-mesenchymal stem cells (MSC). Cell morphology, growth and proliferation were analyzed in?vitro as well as multi-organ engraftment and multilineage differentiation in a murine transplantation model. All scaffolds, except 3D PLGA meshes, supported CB-CD34(+) cell expansion, which was additionally stimulated by UC-MSC support. CB-CD34(+) cells cultured on human-derived 3D fibrin scaffolds with UC-MSC support i) reached the highest overall growth (5?×?10(8)-fold expansion of total nuclear cells after fourteen days and 3?×?10(7)-fold expansion of CD34(+) cells after seven days, p?相似文献   

Pre-differentiated human committed T-lymphoid progenitors promote peripheral T-cell re-constitution after stem cell transplantation in immunodeficient mice

T-cell re-constitution after allogeneic stem cell transplantation (alloSCT) is often dampened by the slow differentiation of human peripheral blood CD34(+) (huCD34(+) ) hematopoietic stem cells (HSCs) into mature T cells. This process may be accelerated by the co-transfer of in vitro-pre-differentiated committed T/NK-lymphoid progenitors (CTLPs). Here, we analysed the developmental potential of huCD34(+) HSCs compared with CTLPs from a third-party donor in a murine NOD-scid IL2Rγ(null) model of humanised chimeric haematopoiesis. CTLPs (CD34(+) lin(-) CD45RA(+) CD7(+) ) could be generated in vitro within 10 days upon co-culture of huCD34(+) or cord blood CD34(+) (CB-CD34) HSCs on murine OP9/N-DLL-1 stroma cells but not in a novel 3-D cell-culture matrix with DLL-1(low) human stroma cells. In both in vitro systems, huCD34(+) and CB-CD34(+) HSCs did not give rise to mature T cells. Upon transfer into 6-wk-old immune-deficient mice, CTLPs alone did not engraft. However, transplantation of CTLPs together with huCD34(+) HSCs resulted in rapid T-cell engraftment in spleen, bone marrow and thymus at day 28. Strikingly, at this early time point mature T cells originated exclusively from CTLPs, whereas descendants of huCD34(+) HSCs still expressed a T-cell-precursor phenotype (CD7(+) CD5(+) CD1a(+/-) ). This strategy to enhance early T-cell re-constitution with ex vivo-pre-differentiated T-lymphoid progenitors could bridge the gap until full T-cell recovery in severely immunocompromised patients after allogeneic stem cell transplantation.     

猕猴骨髓干细胞动员后外周血干细胞、免疫细胞亚群及细胞因子变化

目的:观察GM-CSF动员猕猴骨髓干细胞后外周血干细胞、免疫细胞亚群和细胞因子含量的动态变化,为临床干细胞动员及用于治疗疾病提供参考依据.方法:健康猕猴连续5 d,皮下注射GM-CSF 8 μg/(kg·d),分别于0、2、4、6、8、10 d采集外周血,血细胞分析仪计数白细胞(WBC)总数、淋巴细胞和中性粒细胞比例,流式细胞术(FCM)测定CD34 、CD133 、CD3 、CD4 、CD8 、CD56 细胞比例,酶联免疫分析法测定血清TNF-α、IL-1β、IL-2含量.结果:WBC、中性粒细胞、CD34 、CD133 细胞数量和比例均同步升高(P＜0.01),到动员第6天时达到高峰,细胞数量分别为正常水平的6.4、9.1、117和163.3倍,其中CD34 、CD133 第8天时恢复正常,而WBC、中性粒细胞仍高于正常水平(P＜0.05).CD3 、CD4 、CD8 、CD56 细胞的数量增加,细胞数在第6天时分别为动员前的4.1、4.0、2.9和4.3倍,但比例下降(P＜0.01),到第6天达到最低(P＜0.001),随后逐渐升高至正常以上水平并持续至第10天(P＜0.05).TNF-α、IL-1β、IL-2浓度于动员后6 d内明显升高(P＜0.01),其中TNF-α、IL-1β浓度至8 d恢复正常(P＞0.05),IL-2浓度升高幅度较大并至少持续至第10天(P＜0.01).结论:连续5 d动员猕猴骨髓干细胞可使外周血中CD34 、CD133 细胞比率短暂升高,WBC、中性粒细胞比例持续升高,使CD3 、CD4 、CD8 、CD56 细胞绝对数增加,TNF-α、IL-1β、IL-2浓度升高,表明GM-CSF动员猕猴骨髓干细胞可在细胞和免疫调节因子水平提高免疫功能.     

Ex vivo expansion does not alter the capacity of umbilical cord blood CD34+ cells to generate functional T lymphocytes and dendritic cells

We examined whether ex vivo expansion of umbilical cord blood progenitor cells affected their capacity to generate immune cells such as T lymphocytes (TLs) and dendritic cells (DCs). The capacity to generate TLs from cord blood CD34(+) cells expanded for 14 days (d14) was compared with that of nonexpanded CD34(+) cells (d0) using fetal thymus organ cultures or transfer into nonobese diabetic/severe combined immunodeficient mice. The cell preparations yielded comparable percentages of immature (CD4(+)CD8(-), CD4(+)CD8(+)) TLs and functional mature (CD3(+)CD4(+), CD3(+)CD8(+)) TLs with an analogous TCR (T-cell receptor)-Vbeta repertoire pattern. As regards DCs, d0 and d14 CD34(+) cells also yielded similar percentages of CD1a(+) DCs with the same expression levels of HLA-DR, costimulatory and adhesion molecules, and chemokine receptors. DCs derived from either d14 or d0 CD34(+) stimulated allogeneic TLs to the same extent, and the cytokine pattern production of these allogeneic TLs was similar with no shift toward a predominant Th1 or Th2 response. Even though the intrinsic capacity of d14 CD34(+) cells to generate DCs was 13-fold lower than that of d0 CD34(+) cells, this reduction was offset by the prior amplification of the CD34(+) cells, resulting in the overall production of 15-fold more DCs. These data indicate that ex vivo expansion of CD34(+) cells does not impair T lymphopoiesis nor DC differentiation capacity.     

Importance of stromal determinants in the generation of dendritic and natural killer cells in the human spleen

Summary The interaction between stroma and blood cells in the human spleen has received little attention, despite their well-defined roles during blood cell development in bone marrow. We have reported previously that human spleen-derived fibroblasts display a differentiated myofibroblast phenotype and constitutively express a biologically active form of membrane interleukin (IL)-15 that can drive co-cultured CD34(+) blood cells to differentiate into activated natural killer (NK) cells. Here, we show that, in addition to NK cells, CD34/fibroblast co-cultures also yield myeloid CD1a(+)CD38(+)CD68(+)CD86(+) HLA-DR(+)CD14(-)CD80(-) dendritic cells (DCs) after 3-4 weeks in culture. We found that DC development depended on endogenously secreted stromal macrophage colony-stimulating factor (M-CSF) and CD40/CD40L interaction rather than on fibroblast- and CD34-derived membrane IL-15. CD1a(+) cells were necessary for co-produced NK cells to acquire lytic functions by a mechanism involving cell-to-cell contact and DC-derived IL-12. This study highlights the importance of spleen myofibroblasts in the in vitro generation of two distinct cell types (DC and NK cells) from the innate immune system and suggests that the human spleen is involved in the generation of NK cells from circulating progenitors.     

Reduced levels of both circulating CD4+ CD25+ CD127(low/neg) and CD4+ CD8(neg) invariant natural killer regulatory T cells in stable heart transplant recipients

A cross-regulation between two regulatory T cell (T(reg) ) subsets [CD4(+) CD25(+) and invariant natural killer (NK) T - iNK T] has been described to be important for allograft tolerance induction. However, few studies have evaluated these cellular subsets in stable recipients as correlates of favourable clinical outcome after heart transplantation. T(reg) and iNK T cell levels were assayed by flow cytometry in peripheral blood samples from 44 heart transplant recipients at a 2-year interval in 38 patients, and related to clinical outcome. Multi-parameter flow cytometry used CD4/CD25/CD127 labelling to best identify T(reg) , and a standard CD3/CD4/CD8/Vα24/Vβ11 labelling strategy to appreciate the proportions of iNK T cells. Both subtypes of potentially tolerogenic cells were found to be decreased in stable heart transplant recipients, with similar or further decreased levels after 2 years. Interestingly, the patient who presented with several rejection-suggesting incidents over this period displayed a greater than twofold increase of both cell subsets. These results suggest that CD4(+) CD25(+) CD127(low/neg) T(reg) and iNK T cells could be involved in the local control of organ rejection, by modulating immune responses in situ, in clinically stable patients. The measurement of these cell subsets in peripheral blood could be useful for non-invasive monitoring of heart transplant recipients, especially in the growing context of tolerance-induction trials.     

Altered frequency and phenotype of CD4+ forkhead box protein 3+ T cells and its association with autoantibody production in human immunodeficiency virus-infected paediatric patients

The association between immune dysfunction and the development of autoimmune pathology in patients with human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) is not clear. The frequency and phenotype of regulatory T cells, as well as the presence of autoantibodies, were evaluated in a paediatric cohort of HIV-infected patients without clinical evidence of autoimmune disease. Lower absolute counts but higher percentages of total CD4(+) forkhead box protein 3 (FoxP3)(+) T cells were recorded in children with severe immunosuppression than in those without evidence of immunosuppression. The frequencies of classical CD4(+) CD25(+) FoxP3(+) regulatory T cells were not altered, whereas CD4(+) FoxP3(+) CD25(-) T cells were found increased significantly in patients with severe immunosuppression. Like classical regulatory T cells, CD4(+) FoxP3(+) CD25(-) T cells display higher cytotoxic T-lymphocyte antigen 4 (CTLA-4) but lower CD127 expression compared with CD4(+) FoxP3(-) CD25(+) T cells. An improvement in CD4(+) T cell counts, along with a decrease in viral load, was associated with a decrease in CD4(+) FoxP3(+) CD25(-) T cells. The majority of the patients with severe immunosuppression were positive for at least one out of seven autoantibodies tested and displayed hypergammaglobulinaemia. Conversely, HIV-infected children without evidence of immunosuppression had lower levels of autoantibodies and total immunoglobulins. A decline in CD4(+) FoxP3(+) T cell numbers or a variation in their phenotype may induce a raise in antigen exposure with polyclonal B cell activation, probably contributing to the generation of autoantibodies in the absence of clinical autoimmune disease.     

Ex vivo expansion of megakaryocyte progenitor cells: cord blood versus mobilized peripheral blood

Thrombocytopenia is a problematic and potentially fatal occurrence after transplantation of cord blood stem cells. This problem may be alleviated by infusion of megakaryocyte progenitor cells. Here, we compared the ability of hematopoietic progenitor cells obtained from cord blood and expanded in culture to that of mobilized peripheral blood cells. The CD34(+) cells were plated for 10 days in presence of thrombopoietin (TPO) alone and combined with stem cell factor (SCF), Flt3-ligand (FL), interleukin-3 (IL-3), IL-6, and IL-11. Cells were analyzed for the CD41 and CD42b expression and for their ploidy status. Ex vivo produced platelets were enumerated. We show that (1) TPO alone was able to induce differentiation of CD34(+) cells into CD41(+) cells, with limited total leucocyte expansion; (2) the addition of SCF to TPO decreased significantly CD41(+) cell percentage in CB, but not in MPB; and (3) in CB, the addition of FL, IL-6, and IL-11 to TPO increased the leukocyte expansion with differentiation and terminal maturation into MK lineage. In these conditions, high numbers of immature CD34(+)CD41(+) MK progenitor cells were produced. Our results thereby demonstrate a different sensitivity of CB and MPB cells to SCF, with limited CB MK differentiation. This different sensitivity to SCF (produced constitutively by BM stromal cells) could explain the longer delay of platelet recovery after CB transplant. Nevertheless, in CB, the combination of TPO with FL, IL-6, and IL-11 allows generation of a suitable number of immature MK progenitor cells expressing both CD34 and CD41 antigens, which are supposed to be responsible for the platelet recovery after transplantation.     

Immunostimulatory effects of the anionic alkali mineral complex Barodon on equine lymphocytes

Previous studies have shown that the anionic alkali mineral complex BARODON has an immunoenhancing effect on pigs as an adjuvant and as a nonspecific immunostimulant. Likewise, the equine immune system has been defined with various monoclonal antibodies specific to equine leukocyte differentiation antigens to determine the possibility of enhancing equine resistance to respiratory diseases and promoting other immunostimulatory effects with the application of BARODON. Compared with the control group, after 3 weeks of treatment, BARODON-treated groups showed higher proportions of cells (P < 0.05) expressing major histocompatibility complex class II and CD2, CD4(+), CD4(+) CD25(+), CD8(+), and CD8(+) CD25(+) T lymphocytes, dendritic cells, and surface immunoglobulin M(+) B lymphocytes in peripheral blood, as well as enhanced cell proliferative responses with phytohemagglutinin and increased phagocytic activity against Streptococcus equi and Staphylococcus aureus strains with high antibiotic resistance, the bacteria frequently identified as etiologic agents of equine respiratory diseases at the Seoul Race Park in Seoul, Korea. This study shows that BARODON may act as an immunostimulator and can be an effective alternative to antimicrobial feed additives for nonspecific improvements in equine immune responses, particularly against respiratory diseases.