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PubMed1982

Modulation of T-lymphocyte differentiation antigens: potential relevance for multiple sclerosis.

Effects of the anti-T-cell monoclonal antibodies OKT3, OKT5, and OKT8 on T-cell surface properties and cell functions were evaluated. Incubation of mononuclear cells isolated from peripheral blood for 48 hr with each monoclonal antibody in the absence of complement resulted in modulation of their respective surface antigens; i.e., the number of cells detected by immunofluorescence as positive for the T3, T5, and T8 surface antigens was reduced. T3, T5, and T8 antigens modulated independently. A radiolabeled second antibody technique confirmed modulation by OKT3 and OKT8 and indicated that T-cell differentiation antigens can regenerate in culture. Incubation of mononuclear cells with OKT3 increased the number of sheep erythrocyte-binding lymphocytes (E+-rosetting cells) and markedly increased the number of avidly E+-rosetting cells. Incubation with OKT8 reduced the number of E+- and of avidly E+-rosetting cells. OKT3 induced both mitogenic reactivity and suppressor cell activity; cells modulated by OKT8 exhibited reduced mitogenic reactivity and reduced suppressor cell function. The decreases in total T cells, in avid T cells, in suppressor cell number, and in suppressor cell function that follow modulation by OKT8 mimic changes observed in multiple sclerosis patients.

Adult↗
PubMed1993

Modulation of cell surface antigens and regulation of phagocytic activity mediated by CD11b in the monocyte-like cell line U937 in response to lipopolysaccharide.

Modulation of the cellular antigens and regulation of the phagocytic activity of the monocyte-like cell line U937 after culture with lipopolysaccharide (LPS) were investigated. CD14 expression was induced on the surface of the U937 cells after 48 h of culture with LPS and then they became adhesive with numerous filamentous filopodia extruded on the cell surface, exhibiting the enhanced expression of CD16 and CD23, the activation cell surface markers for differentiation into macrophage. However, no induction or enhancement of the cell surface expression was observed with respect to CD11b, CD18, HLA-A, B, C, HLA-DR, DQ, DP or CD57. These U937 cells also acquired the ability to produce superoxide anions and to phagocytose the Salmonella enteritidis strain, 116-54. This phagocytosis was inhibited by the anti-CD11b monoclonal antibodies, but not by the anti-CD14, anti-CD16, anti-CD18, anti-CD23, anti-HLA-A, B, C or anti-HLA-DR monoclonal antibodies. These findings indicate that the phagocytic activity against Salmonella enteritidis 116-54 induced by LPS is mediated mainly via the CD11b molecule, but is not associated with the increased expression of CD11b. Puromycin and cycloheximide, inhibitors of protein synthesis, or a divalent cation-chelating agent, EDTA completely inhibited this phagocytic activity. Interestingly, EDTA was found to suppress specifically the CD11b expression on the U937 cells cultured with LPS. No phagocytic activity was induced when the U937 cells cultured with LPS were incubated at 4 degrees C, but restored to the control level when shifted up to 37 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens, CD↗
PubMed1987

Antibody-induced modulation of H-2Kb antigens on mouse tumor cells in vitro.

Modulation of H-2Kb antigens on cells of a subline of the murine Lewis lung carcinoma was induced in vitro by a monoclonal antibody with specificity for H-2Kb antigens. High antibody concentrations resulted in a more spherical morphology of the cells, in a discrete loss of all antibody-antigen complexes within 4-6 hr, and in a corresponding maximal decrease in the total cellular antigen content 6-8 hr after antibody exposure. Restoration was complete within 2 hr after removal of the complexed antigen and occurred without any visible cap formation.

Animals↗
PubMed2001

Modulating cell surface immunoreactivity by metabolic induction of unnatural carbohydrate antigens.

BACKGROUND: Sialic acid is a component of many tumor-associated oligosaccharide antigens. The repertoire of sialic acids presented by cells can be expanded to include unnatural variants by intercepting the sialic acid biosynthetic pathway with unnatural precursors. We explored whether unnatural cell surface sialosides produced by metabolism can act as neo-antigens and modulate the immunogenicity of cells. RESULTS: Immunization of rabbits with synthetic conjugates of an unnatural sialic acid bound to keyhole limpet hemocyanin produced significant titers of antibodies that were specific for the structurally altered sialic acid. The antibodies recognized cells that were fed the unnatural biosynthetic precursor, and were capable of directing complement-mediated lysis. CONCLUSIONS: Structural alteration of sialic acids replaces a tolerized self-antigen with an antigenic determinant. Incorporation of unnatural sialosides into cell surface glycoconjugates through biosynthetic means can alter the immunoreactivity of cells, providing new possibilities for tumor immunotherapy.

Adjuvants, Immunologic↗
PubMed1997

Corticosteroid modulation of human, antigen-specific Th1 and Th2 responses.

Corticosteroids are potent antiinflammatory agents that modulate human T-lymphocyte responses. Controversy remains as to their possible differential effects on Th1 and Th2 subsets. This study explores the kinetics and efficacy of these agents in human, antigen-driven peripheral blood mononuclear cells (PBMCs) and in nontransformed, antigen-specific Th1 and Th2 clones. Ragweed- and tetanus toxoid-driven proliferative responses of PBMCs from dually sensitized individuals were downregulated equally by dexamethasone (inhibitory concentration of 50% [IC(50)] = 3 x 10(-9) and 2 x 10(-9) mol/L, respectively). The addition of dexamethasone as late as 36 hours after ragweed stimulation still resulted in more than 75% inhibition of the proliferative response, whereas the efficacy of dexamethasone was less than 50% when added 24 hours after tetanus toxoid stimulation. Antigen-induced gene expression for proinflammatory cytokines (IL-4, IL-5, IL-13, and interferon-gamma) from PBMCs was also downregulated by dexamethasone. Proliferation of antigen-specific Th1 and Th2 clones was inhibited by several corticosteroids (hydrocortisone < budesonide < dexamethasone; IC(50) = 10(-6) to 10(-8) mol/L), but no significant differences between Th1 and Th2 clones were evident. IC(50) values in the clones were 10-fold greater than in PBMCs. Gene expression and protein secretion for IL-4, IL-13, and interferon-gamma were downregulated in a concentration-dependent manner by each of the corticosteroids in Th1 and Th2 clones. These data suggest that Th1 and Th2 responses are equally affected by corticosteroids.

Adrenal Cortex Hormones↗
PubMed1990

Human ciliated bronchial epithelial cells: expression of the HLA-DR antigens and of the HLA-DR alpha gene, modulation of the HLA-DR antigens by gamma-interferon and antigen-presenting function in the mixed leukocyte reaction.

HLA-DR class II molecules are expressed by a variety of nonlymphoid cells, including the respiratory epithelium. However, it is not known if ciliated bronchial epithelial cells express the HLA-DR genes, if the expression of class II molecules on their surface can be modulated by immune mediators and, finally, if these cells, like other HLA-DR-positive epithelial cells, have the potential to serve as antigen-presenting cells. To answer these questions, we collected ciliated bronchial epithelial cells by brushing and by suction during fiberoptic bronchoscopy and by scraping surgically resected bronchi. The number of cells recovered by brushing or suction during fiberoptic bronchoscopy was similar (P greater than 0.2), but lower than that obtained by scraping surgically resected bronchi (P less than 0.01); however, compared with brushing, suction of ciliated bronchial epithelial cells resulted in a better viability (P less than 0.05). HLA-DR antigens on ciliated bronchial epithelial cells were detected by immunofluorescence using the PTF 29.12 and the L243 monoclonal antibodies, both recognizing HLA-DR molecules on the vast majority of ciliated bronchial epithelial cells. Cytoplasmic dot blot analysis demonstrated that ciliated bronchial epithelial cells had mRNA HLA-DR transcripts, and Northern blot hybridizations showed that the size of the HLA-DR messages was the same observed in other HLA-DR-positive cells. Interestingly, ciliated bronchial epithelial cells showed a significant decline of HLA-DR expression after 5 days in culture, but the addition of gamma-interferon to the cell cultures was associated with the persistence of the expression of class II antigens on the cell surface (P less than 0.01 with control cultures at 5 days). Finally, while ciliated bronchial epithelial cells were ineffective in stimulating allogeneic T cell proliferation in a 6-day primary mixed leukocyte reaction (MLR), the addition of phorbol myristate acetate to the MLR was able to induce a significant T cell proliferation (P less than 0.001, all comparisons). Thus, human ciliated bronchial epithelial cells express HLA-DR surface antigens and have mRNA molecules for the HLA-DR genes, and the expression of the surface class II antigens can be modulated in vitro by immune mediators.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1986

CD 1-8 antigens on human diphtheria toxoid T lymphocyte clones: expression and modulation by TPA, sodium butyrate, and 5-azacytidine.

The modulation of antigen expression on the surface of TLC by different differentiation inducers as well as the inhibition of the TLC proliferative response by specific MoAbs may lead to a clarification of the role of various surface molecules studied in antigen-specific T-cell response. We investigated the expression of CD 1-8 antigens on the surface of diphtheria toxoid or varidase specific TLC with a series of MoAb. CD1 and CD8 antigens were not expressed on the proliferative TLC. CD2, CD3, CD4, and CD5 antigens were homogeneously expressed on all TLC in contrast to CD6 and CD7 antigens which were present on only a fraction of the cells in a given TLC. In functional assays, anti-CD2, anti-DR VI-15C, and anti-CD25 MoAbs blocked the proliferative response to DT and anti-CD3, anti-CD4, anti-D44 MoAbs had intermediate inhibition effects. Anti-CD5, anti-CD6, and anti-CD7 MoAbs did not inhibit the proliferative response. Surface marker analysis revealed that the expression of CD2 to CD7 antigens (and also CD25) may be modified following incubation of the TLC with TPA or sodium butyrate but not with 5-azacytidine. TPA greatly decreased the expression of CD3 and CD4 antigens after a 6-hr exposure. Preincubation of TLC cells with TPA inhibited the mitogenic effect of anti-CD3 MoAbs on TLC cells in proliferative assays, but did not inhibit their capacity to proliferate in response to DT despite low levels of CD3 and CD4.

Antibodies, Monoclonal↗
PubMed1991

A signal transduction through a unique rat T cell specific antigen, 8H3.

A signal transduction was detected in various rat T cells by cross-linking of 8H3 antigen by 8H3 antibody. A rat T cell proliferative response induced by 8H3 antibody is dependent on the presence of adherent cells. When spleen cells were cultured in the presence of 8H3 antibody, only CD4-positive T cell proliferation was induced. These proliferative CD4-positive T cells express rat interleukin 2 receptor, alpha chain. Cross-linking of 8H3 antigen resulted in an increase in cytoplasmic free Ca2+ in T cells and phosphorylation of a 120 kDa component of the 8H3 antigen. It should be noted that cross-linking of 8H3 antigen together with CD4 antigen but not with CD8 antigen by suboptimal doses of 8H3 and corresponding antibodies initiated the mobilization of [Ca2+]i. Furthermore, physical association of 8H3 antigen with TCR was demonstrated by comodulation of these two molecular complexes in some T cells. Thus, 8H3 antigen is involved in rat T cell transmembrane signal transduction.

Animals↗
PubMed1994

H blood group antigen carried by CD44V modulates tumorigenicity of rat colon carcinoma cells.

Expression of carbohydrate ABH blood group antigens is oncodevelopmentally regulated and their presence on tumor cells constitutes a prognostic factor. However, it is not clear whether they directly affect tumor behavior. Using a rat model of colon carcinoma, we previously observed an association between the presence of H blood group antigens and tumorigenicity in syngeneic animals. In the present study, we show by immunoprecipitation experiments that cell surface H blood group antigens of a highly tumorigenic clone (PROb) are essentially carried by splice variants of the CD44 molecule containing exon V6. PROb cells were then transfected with an antisense fragment of the gene coding for a rat alpha (1-2)fucosyltransferase. This enzyme allows synthesis of H antigens from various beta-galactoside precursors. Transfected subclones of PROb cells were obtained which had significantly decreased enzymatic activity and H antigenic cell surface levels. In contrast, no such changes were observed in control cells transfected with either the empty vector or with a sense fragment of the gene. Compared to controls, the antisense-transfected cells were far less tumorigenic in syngeneic animals. These results show that H blood group antigens at the surface of PROb colon carcinoma cells contribute to tumor progression. The presence of the fucosylated structures on CD44 could modulate the functions of this adhesion molecule.

ABO Blood-Group System↗
PubMed2006

Chemokine receptor expression and modulation by Mycobacterium tuberculosis antigens on mononuclear cells from human lymphoid tissues.

Chemokine receptor switching on lymphoid cells is an important factor regulating migration and homing, but little is known about the expression of such molecules during Mycobacterium tuberculosis infection in humans. We describe CCR2, CCR5 and CCR7 expression on human cells from blood, spleen and pulmonary hilar lymph nodes (PHLN) stimulated by M. tuberculosis antigens. CCR2 was not expressed by CD3+ cells regardless of the presence of antigen, but was highly expressed on CD14+ CD63+ monocytes/macrophages. CCR2 decreased on splenic monocytes/macrophages by nearly 50% in culture, independent of antigen, but remained high in blood and PHLN. CCR5 was low in CD3+ cells and was down-regulated by M. tuberculosis antigens on blood and splenic cells but not in PHLN. CCR5 was highly expressed on monocytes/macrophages and was down-regulated by M. tuberculosis antigens at 48 hr only in blood. Less than 15% of CD3+ cells from spleen and PHLN were CCR7+, whereas nearly 40% from blood expressed this receptor on primary isolation. However, CCR7 in PHLN increased in culture, independent of antigen. Monocytes/macrophages did not express CCR7. Thus, we characterize, for the first time, chemokine receptor expression and differential modulation by M. tuberculosis antigens on human mononuclear cells from spleen, blood and PHLN. Knowledge of chemokine receptor switching in human lymphoid tissue provides novel insight into mechanisms of the immune response to M. tuberculosis with potential effects on directing cell trafficking.

Adolescent↗
PubMed1984

Modulation of cell surface antigens induced by 12-O-tetradecanoyl-phorbol 13-acetate in two myeloblastic cell lines, a promyelocytic cell line, and a monoblastic cell line: detection with five monoclonal antibodies.

The modulation of cell surface antigens in 2 myeloblastic cell lines (ML-1 and KG-1), a promyelocytic cell line (HL-60), and a monoblastic cell line (THP-1-0) by the presence of 12-O-tetradecanoyl-phorbol 13-acetate [(TPA) CAS: 16561-29-8] was investigated by indirect membrane immunofluorescence with the use of three monoclonal antibodies (MoAb) (OKM-1, 63D3, and MCS-2) reacting with myeloid-monocyte antigens (expressed by cells of both granulocyte and monocyte lineages) and two MoAb (1/12/13 and MCS-1) reacting with myeloid antigens (expressed by cells of the granulocyte lineage). Functionally mature macrophage properties, such as adherence, morphologic character, and phagocytosis, were induced by the presence of TPA in each of the cell lines except for adherence in the HL-60 cells. After 3 days in culture, the expression of the OKM-1-defined antigen was markedly augmented in all 4 cell lines. The expression of the 63D3-defined antigen was also markedly augmented in the ML-1, KG-1, and THP-1-0 cells, but it was not significantly altered in the HL-60 cells. The MCS-2-defined antigen was amplified in expression in the ML-1 and HL-60 cells, but it showed minimum decrease in the KG-1 and THP-1-0 cells. The MCS-1-defined antigen expression was suppressed in ML-1, HL-60, and THP-1-0 but was enhanced in KG-1. The suppressed expression of My-1 antigen (detected by the MoAb 1/12/13) was noted in all 4 cell lines. Thus in the ML-1 cells, expression of the myeloid-monocyte antigens was augmented, whereas myeloid antigen expression was inhibited in the presence of TPA, a result that parallels antigenic expression in terminal macrophage differentiation. The trend was true, except for the 4 cell line-antigen combinations (MCS-2-defined antigen and MCS-1-defined antigen in KG-1, 63D3-defined antigen in HL-60, and MCS-2-defined antigen in THP-1-0). The heterogeneous attitude of some antigens to TPA found in these cell lines may result from the fact that they represent different points in the myeloid-monocyte differentiation scheme.

Antibodies, Monoclonal↗
PubMed1995

Moloney leukemia virus-induced cell surface antigen mimicry by monoclonal antibodies.

We have investigated antigen-independent modulation of immune responses by monoclonal antibodies directed against both viral and nonviral antigens. BALB/c mice were immunized with monoclonal IgM (i.e. Ab1) specific for either Moloney murine leukemia virus-induced cell surface antigen (MCSA) or the hapten 2,4-dinitrophenyl (DNP). Injection with either Ab1 activated a functional idiotypic (Id) network as evidenced by production of both anti-Id (Ab2) antibodies and anti-anti-Id (Ab3) antibodies. A subset of induced Ab3 (designated Ab1'), exhibited specificity for antigen (virus or DNP). In mice immunized with anti-Id antibodies (Ab2), production of Ab3 and Ab1' was also observed. In the MCSA system, antibody-induced Ab1' responses were effective in protecting mice from tumor development upon subsequent challenge with live virus. Furthermore, antigen-independent modulation of immunity to both viral and nonviral antigens was found to be thymus-dependent. Similar findings in other viral systems suggest that antibody-induced activation of Id networks may prove a viable alternative vaccine strategy that can elicit antigen-specific responses, and in some cases protection, in the apparent absence of exposure to antigen.

Animals↗
PubMed1986

Modulation of surface T11 molecules induced by monoclonal antibodies: analysis of the functional relationship between antigen-dependent and antigen-independent pathways of human T cell activation.

Previous data indicated that T lymphocyte activation can be achieved by using a combination of anti-T11 monoclonal antibodies (mAb) directed to the "T11(2)" and the "T11(3)" epitopes, respectively. Unlike the T cell activation induced by antibodies directed to the T3-T cell receptor (Ti) complex or to T44 molecules, the anti-T11 mAb-induced cell activation was not accompanied by surface modulation of the T11 antigen. In the present study we show that appropriate stimulatory combinations of anti-T11 mAb are able to induce T11 antigen modulation in a variety of T cells including polyclonal peripheral blood populations, normal as well as leukemic (JA3) T cell clones. The first anti-T11 mAb combination leading to both cell activation and T11 antigen modulation was given by a mAb directed to the T11(2) epitope and by another mAb recognizing an epitope belonging to the T11(1) group. The second combination was given by two mAb directed against two different determinants of the T11(1) group. The ability to induce T11 antigen modulation allowed a more precise analysis of the pathway of T cell activation initiated by T11 molecules and its physical and functional relationship with the other known pathways of T cell activation. T cells following T11 antigen modulation failed to respond to subsequent stimulation with anti-T11 mAb. The refractory period lasted for 48-72 h and the restoration of the responsiveness to anti-T11 mAb coincided with the re-expression of T11 molecules at the cell surface. Modulation of T11 antigen did not affect the surface expression of T3, Ti or T44 molecules, in addition, "modulated" cells maintained their ability to respond to mAb directed against T3, Ti or T44 molecules. On the contrary, antibody-induced modulation of the T3-Ti receptor complex abrogated both T11- and T44-dependent T cell activation. Finally, antibody-induced modulation of T44 antigen did not inhibit either the T11- or the T3-Ti-dependent pathway of T cell activation. These data indicate that down-regulation of the pathway of T cell activation initiated by T11 molecules can be induced not only by modulation of the antigen receptor complex but also by appropriate mAb to T11 molecules and, presumably, by the natural ligand binding to T11 molecules.

Antibodies, Monoclonal↗
PubMed1993

Histamine N-methyltransferase modulates histamine- and antigen-induced bronchoconstriction in guinea pigs in vivo.

To examine whether histamine N-methyltransferase (HMT; EC 2.1.1.8) modulates the effects of allergic reaction in vivo, we studied the effects of aerosolized SKF 91488, a specific HMT inhibitor, on the responses to aerosolized histamine in unsensitized guinea pigs and to ovalbumin (OA) antigen inhalation in guinea pigs sensitized to OA. Airway responsiveness was assessed by determining provocation concentrations of histamine and OA aerosols that increased pulmonary resistance to twice the baseline values. SKF 94188 shifted, in a dose-dependent fashion, the dose-response curves to histamine and OA antigen to lower concentrations, and it significantly decreased provocation concentrations of both histamine and OA antigen (p < 0.01). In contrast of SKF 91488, aerosolized aminoguanidine, a specific inhibitor of diamine oxidase (10(-2) M, 90 breaths), did not alter the provocation concentration of histamine (p > 0.20). SKF 91488 (10(-2) M, 90 breaths) caused no significant changes in response to acetylcholine (p > 0.30). HMT activities were observed in the entire airways of the trachea, main bronchi, segmental bronchi and bronchioles, and parenchymal tissues. These findings suggest that HMT modulates the effects of exogenous histamine and endogenously released histamine by antigen challenge on bronchoconstrictor responses in guinea pigs in vivo.

Aerosols↗
PubMed1985

Monoclonal anti-actin antibody modulates expression of surface antigen on L cells.

Monoclonal anti-actin antibody which is known to stimulate DNA synthesis and cell growth in a murine transformed cell line, L cell, was examined for its ability to modulate the expression of surface antigen on the cell membrane. There was a time dependent increase in the number of cell surface antigen molecules on L cells stimulated by monoclonal anti-actin antibody as measured by indirect immunofluorescence and flow cytometry. For L cells incubated for 12, 24, 48, 72, and 96 hours with monoclonal anti-actin antibody versus a myeloma control supernatant, the percentage of cells exhibiting high intensity immunofluorescence was 29 vs. 13, 13 vs. 10, 34 vs. 1, 52 vs. 11, and 35 vs. 18, respectively. We conclude that monoclonal anti-actin antibody modulates the time dependent surface expression of actin on L cells. It is likely that this modulated expression of surface actin-like molecules plays an important role in the transmission of stimulatory signals to the cells which result in enhanced cellular metabolism and proliferation.

Actins↗
PubMed1992

Modulation of ovarian carcinoma OV632 antigen by interferons.

Interferons are known to modulate several cellular functions by the induction of different proteins. In our study interferon-gamma and -alpha augmented presentation of one specific ovarian cancer antigen recognized by the antibody OV632 on the cell surface on one of four ovarian carcinoma cell lines in vitro (HTB-77). The interferon-gamma effect reached a maximum after 24 of treatment. Both HLA-DR and OV632 antigen expression were increased by interferon-gamma on HTB-77 cells whereas the two cell lines OVCAR-3 and 2780, which respond to an interferon-gamma treatment with a reduced proliferation and induction of HLA-DR, and also the interferon-resistant CRL-1572 were found to be resistant regarding OV632 epitope modulation. The demonstration of OV632 expression provides an important insight into the potential regulatory mechanism governing this tumor marker.

Antigens, Neoplasm↗
PubMed2004

Immune response to a major Trypanosoma cruzi antigen, cruzipain, is differentially modulated in C57BL/6 and BALB/c mice.

BALB/c mice immunized with cruzipain, a major Trypanosoma cruzi antigen, produce specific and autoreactive immune responses against heart myosin, associated with cardiac functional and structural abnormalities. Preferential activation of the Th2 phenotype and an increase in cell populations expressing CD19+, Mac-1+ and Gr-1+ markers were found in the spleens of these mice. The aim of the present study was to investigate whether cardiac autoimmunity could be induced by cruzipain immunization of C57BL/6 mice and to compare the immune response elicited with that of BALB/c mice. We demonstrate that immune C57BL/6 splenocytes, re-stimulated in vitro with cruzipain, produced high levels of IFNgamma and low levels of IL-4 compatible with a Th1 profile. In contrast to BALB/c mice, spleens from cruzipain immune C57BL/6 mice revealed no significant changes in the number of cells presenting CD19+, Mac-1+ and Gr-1+ markers. An increased secretion of TGFbeta and a greater number of CD4+ TGFbeta+ cells were found in immune C57BL/6 but not in BALB/c mice. These findings were associated with the lack of autoreactive response against heart myosin and a myosin- or cruzipain-derived peptide. Thus, the differential immune response elicited in C57BL/6 and BALB/c mice upon cruzipain immunization is implicated in the resistance or pathogenesis of experimental Chagas' disease.

Animals↗
PubMed1998

Fate of antigen in xenotransplantation: implications for acute vascular rejection and accommodation.

Antigen down-modulation plays a critical role in xenotransplants involving humoral responses against the Forssman antigen and may play a role in the long-term survival of ABO-incompatible allografts. The present study investigates the fate of porcine antigens in pig-to-primate xenotransplantation. Human antibodies bound to the glycocalyx of cultured porcine aortic endothelial cells as judged by electron microscopy and were shed from the cell surface in a complex with fibronectin, a glycoprotein that is found in the apical membrane glycocalyx of cultured cells. Antibody was shed in a metabolically dependent process with a t(1/2) of 2 to 3 hours. However, the amount of antigen on the cell surface did not change appreciably within 24 hours, suggesting that antigen modulation did not occur. Over the ensuing days, antigen expression decreased, although the change was always less than 50% of baseline. Changes in antigen expression were due for the most part to changes in expression of alpha-galactosyl residues. Consistent with results obtained in vitro, antigen expression in porcine organ transplants remained at approximately the baseline level as determined by immunofluorescence analysis of IgM binding to graft endothelium. If, as these results suggest, antigen is not down-modulated in pig-to-primate xenotransplantation, then therapies aimed at prolonged xenograft survival must focus on antibody or genetic manipulation of antigen expression.

Animals↗