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F A Zuckermann

Publications and source records attributed to F A Zuckermann.

At least 37 records · Page 2Linked to original sources
PubMed1996

Distribution of porcine CD4/CD8 double-positive T lymphocytes in mucosa-associated lymphoid tissues.

The present study describes the distribution of CD4/CD8 double-positive (DP) T cells in lymph nodes and mucosa-associated lymphoid tissues of pigs at 6-7 months of age. Proportions of lymphocytes isolated from peripheral, bronchial and mesenteric lymph nodes expressing CD4 and/or CD8 molecules were similar and ranged from 10-13% CD4/CD8 DP cells, 25-27% CD4 single-positive (SP) cells, and 27-32% CD8 SP cells. Mucosa-associated lymphoid tissues had significantly smaller proportions of CD4+ and/or CD8+ T cells than lymph nodes and CD4/CD8 DP cells accounted for a larger proportion of the total CD4+ lymphocytes than in lymph nodes. Compared to the lymph nodes, the predominant CD4+ and/or CD8+ T-cell subset in tonsils was the CD4/CD8 DP population (18%), because of both a higher proportion of these cells and a lower proportion of CD4 SP (12%) and CD8 SP (14%) lymphocyte subsets. Jejunal Peyer's patches were comprised of 12% CD4 SP, 28% CD8 SP and 10% CD4/CD8 DP lymphocytes. In contrast, the mid-section of the continuous Peyer's patch in the ileum contained 7% CD4 SP, 8% CD8 SP and 4% CD4/CD8 DP lymphocytes. The distribution of T lymphocytes in porcine mucosal lymphoid aggregates agrees with the reported correlation between high and low rates of lymphocyte entry into these tissues and the abundance or scarcity of T cells, respectively. Defining the role of CD4/CD8 DP lymphocytes and their unique distribution in mucosa-associated lymphoid tissues in the pig may reveal novel T-cell-mediated regulatory pathways.

Animals↗
PubMed1996

Functional and phenotypic analysis of porcine peripheral blood CD4/CD8 double-positive T cells.

Functional and phenotypic properties of porcine peripheral blood CD4/CD8 double-positive (DP) lymphocytes were examined. In cross-sectional and longitudinal studies involving a total of 103 pigs, this lymphocyte population was found to increase gradually in proportion with age, comprising < 2% of the total peripheral blood lymphocyte pool in 1-week-old swine and reaching 30-55% by 3 years of age. CD4/CD8 DP lymphocytes were able to proliferate in response to stimulation with recall viral antigen. Furthermore, these cells mostly expressed high levels of the surface antigen recognized by monoclonal antibody (mAb) 4B4 (4B4hi), which is specific for the human beta 1 integrin. The CD4+4B4hi lymphocytes from pseudorabies virus-immune swine, proliferated in response to stimulation with the homologous virus, while CD4+4B4lo lymphocytes did not. Stimulation of CD4 single-positive (SP) cells with recall viral antigen, but not with mitogen, resulted in the generation of lymphoblasts which were predominantly of CD4/CD8 DP phenotype, suggesting a role for recall antigen in the generation of this lymphocyte subset. More than half of the CD4+ lymphocytes from palatine tonsils of 6-month-old swine were CD4/CD8 DP, while in the lymph nodes CD4/CD8 DP cells accounted for only one-third or less of CD4+ cells. In contrast, CD4/CD8 DP lymphocytes were absent from the palatine tonsils of 3-day-old swine, which only contained CD4 SP cells. Together, these results indicate that porcine CD4/CD8 DP lymphocytes, exhibit properties of mature antigen-experienced cells, and are inducible by stimulation with recall antigen. These data are consistent with the hypothesis that this population in swine includes memory/effector T cells.

Age Factors↗
PubMed1995

Use of corticosteroids and aurothioglucose in a pygmy goat with pemphigus foliaceus.

Pemphigus foliaceus was diagnosed in a 20-month-old female pygmy goat. The goat had a 3-month history of chronic exfoliative dermatitis and was examined after developing alopecia and severe, asymmetric, diffuse flakes of dry, nonadherent skin scales. Pemphigus foliaceus was diagnosed on the basis of dermatohistologic findings and was confirmed by analysis of results of direct immunofluorescence testing of perilesional specimens obtained by use of a punch biopsy. The goat was successfully treated with prednisolone (immunosuppressive induction dosage; 1 mg/kg of body weight, IM, q 12 h). Remission was achieved in 1 week and was maintained by use of prednisolone (immunosuppressive maintenance dosage; 1 mg/kg, IM, q 48 h). Treatment with aurothioglucose (1 mg/kg, IM, q 7 d) that was initiated during administration of prednisolone and was continued after discontinuation of corticosteroid administration failed to prevent redevelopment of pemphigus foliaceus.

Alopecia↗
PubMed1994

Porcine peripheral blood CD4+/CD8+ dual expressing T-cells.

The porcine T-cell population is unique in that there is a large percentage of CD+CD8+ dual expressing peripheral T-cells. This paper reviews the data available on these porcine T-cells and compares them to the much rarer dual expressing T-cells in humans. The percent of dual expressing cells increases with activation in in vitro culture with various antigens including pseudorabies virus. The percent of resting dual expressing cells also increases with the age of the pig. Flow-cytometric-sorted dual expressing cells responded in culture to the super antigen staphylococcal enterotoxin B. Selected CD4+CD8- cells cultured in vitro developed expression of CD8 and maintained the dual expressing phenotype for the 12 weeks of culture. Dual expressing cells freshly prepared from porcine blood did not express the IL-2 receptor as demonstrated by their failure to bind FITC-IL-2 and an anti-porcine IL-2 receptor monoclonal antibody. In response to activation with phorbol myristic acetate, CD4, but not CD8, was down regulated on the dual expressing T-cells. In summary, porcine dual expressing T-cells constitute a substantial percentage of the porcine peripheral T-cell pool. These cells appear to contain the majority of the memory T-cell with their frequency increasing with blood donor age and in vitro culture. Although the receptor specificity is not known, they have a functional receptor. Finally, the function of the two accessory molecules CD4 and CD8 in these cells is not known, but their regulation is distinct, thereby suggesting no equivalent roles in immune function.

Animals↗
PubMed1994

Analyses of monoclonal antibodies reactive with porcine CD44 and CD45.

Twenty-six monoclonal antibodies (mAbs), assigned to the CD44/CD45 section of the First International Swine CD Workshop, were compared for their reactivity against a selected group of target cells by one- and two-color flow cytometric analysis. Based on staining and reactivity patterns the 26 mAbs were assigned to six groups, group F1 mAbs were designated CD44 mAbs; and groups F2 and F3 as CD45 mAbs. With the information available, a CD designation could not be given to the mAbs in groups F4, F5 or F6 consisting of four, three and four mAbs each, respectively. The reactivity of all six mAbs in group F1 (MAC35, 25-32, PORC24A, H22A, BAG40A, and BAT31A) was blocked by soluble porcine CD44. One mAb in this group (MAC325) reacted with a cell surface protein with a molecular weight of 80 kDa and was designated as CD44; the other five mAbs were designated as wCD44 because no molecular weight was known. Blocking experiments utilizing a cross reactive anti-human CD44 (mAb Z062) allowed the definition of the wCD44a epitope recognized by mAbs PORC24A and H22A. The group F2 mAbs (74-9-3; MAC323; K252.1E4; and 2A5) were designated as CD45 based on their broad reactivity pattern with lymphoid and myeloid cells and their ability to immunoprecipitate three polypeptides with an apparent molecular weight of 226, 210 and 190 kDa. The F3 mAbs (MAC327; MAC326; 3a56 and -a2) were designated as CD45R based on their restricted reactivity against lymphoid and myeloid target cells, and their ability to immunoprecipitate either two polypeptides with an apparent molecular weight of 226 and 210 kDa (mAbs MAC327 and MAC326) or a single polypeptide with an apparent molecular weight of 210 kDa (mAbs-a2 and 3a56). Sequential immunoprecipitation analyses confirmed the relatedness of the F2 and F3 group mAbs. The work conducted for this first workshop led to the definition of six mAbs specific for CD44, four mAbs specific for CD45, and four mAbs specific for CD45R which should prove to be very valuable reagents for the study of the porcine immune system.

Animals↗
PubMed1994

Biochemical analysis of molecules reactive with monoclonal antibodies specific for porcine CD45.

The apparent molecular weight of molecules reactive with eight mAbs, which were identified during the First International Swine CD Workshop as putatively specific for porcine CD45, was determined by immunoprecipitation analysis of 125I surface-labeled peripheral blood mononuclear cells. Four putative CD45 specific mAbs (K252.1E4, MAC323, 74-9-3 and 2A5) precipitated three polypeptides of 226, 210 and 190 kDa. Two putative CD45R specific mAbs (MAC326 and MAC327) precipitated two polypeptides with an apparent molecular weight of 226 and 210 kDa, while another two (3a56 and -a2) precipitated a single polypeptide of 210 kDa. Sequential immunoprecipitations analyses indicated that the comigrating molecules precipitated by the CD45 and CD45R were the same. The results from this study confirmed the assignment of mAbs K252.1E4, MAC323, 74-9-3 and 2A5 as CD45, and mAbs MAC326, MAC327, 3a56 and -a2, as CD45R. These CD45 and CD45R specific mAbs should prove to be valuable reagents for the study of the porcine immune system.

Animals↗
PubMed1992

Apparent retrovirus-induced immunosuppression in a yearling llama.

Immunosuppression suspected to be associated with retrovirus infection was diagnosed in an 18-month-old female llama. The llama had a 6-month history of weight loss, intermittent lameness, and infections that were nonresponsive to treatment. Serial CBC indicated persistent nonregenerative anemia and leukopenia characterized by absolute neutropenia and lymphopenia. Functional hypoplasia of myeloid and erythroid cell lines was detected in serial bone marrow biopsy specimens. Notable pathologic findings included inadequate hematopoiesis, generalized lymphoid hypoplasia and plasma cell depletion, and pulmonary alveolar histiocytosis. Pneumocystis carinii cysts and viral particles of the size and morphologic features consistent with the retrovirus family were observed in lung sections examined by transmission electron microscopy. Antemortem macrophage and postmortem lymph node cultures were positive for reverse transcriptase activity.

Animals↗
PubMed1991

Sensitivity of the standardized pseudorabies virus neutralization test varies with the test strain used.

The effect of altering the strain of the test virus used in the standardized pseudorabies virus neutralization (VN) test on the sensitivity of the assay was evaluated. Comparative VN tests were performed using 4 different strains: the avirulent Bartha parental, the avirulent recombinant Bartha gIIIKa, the moderately virulent Shope (currently used for the VN test at the National Veterinary Services Laboratory, Ames, IA), and the highly virulent P2208 (Funkhauser). A radioimmunoassay and a Western immunoblotting technique were employed to verify the presence of anti-pseudorabies virus (PrV) antibodies in sera. Statistical analysis indicated that replacement of the Shope strain by the Bartha gIIIKa or the P2208 strain resulted in VN titers that were 4.23- and 2.00-fold higher, respectively. Despite these differences, specificity with regard to PrV diagnosis was unaltered. This apparent enhancement of the sensitivity of the PrV VN test would be beneficial for the serologic identification of PrV-infected animals during an eradication effort.

Animals↗
PubMed1990

Pseudorabies virus glycoprotein gIII is a major target antigen for murine and swine virus-specific cytotoxic T lymphocytes.

Pseudorabies virus (PrV) is the etiological agent of Aujeszky's disease, a disease that causes heavy economic losses in the swine industry. A rational approach to the generation of an effective vaccine against this virus requires an understanding of the immune response induced by it and of the role of the various viral antigens in inducing such a response. We have constructed mutants of PrV [strain PrV (Ka)] that differ from each other only in expression of the viral nonessential glycoproteins gI, gp63, gX, and gIII (i.e., are otherwise isogenic). These mutants were used to ascertain the importance of each of the nonessential glycoproteins in eliciting a PrV-specific cytotoxic T-lymphocyte (CTL) response in mice and pigs. Immunization of DBA/2 mice and pigs with a thymidine kinase-deficient (TK-) mutant of PrV elicits the formation of cytotoxic cells that specifically lyse syngeneic infected target cells. These PrV-specific cytolytic cells have the phenotype of major histocompatibility complex class I antigen-restricted CTLs. The relative number of CTLs specific for glycoproteins gI, gp63, gX, and gIII induced in mice vaccinated with a TK- mutant of PrV was ascertained by comparing their levels of cytotoxicity against syngeneic cells infected with either wild-type virus or gI-/gp63-, gX-, or gIII- virus deletion mutants. The PrV-specific CLTs were significantly less effective in lysing gIII(-)-infected targets than in lysing gI-/gp63-, gX-, or wild-type-infected targets. The in vitro secondary CTL response of lymphocytes obtained from either mice or pigs 6 or more weeks after immunization with a TK- mutant of PrV was also tested. Lymphocytes obtained from these animals were cultured with different glycoprotein-deficient mutants of PrV, and their cytolytic activities against wild-type-infected targets were ascertained. The importance of each of the nonessential viral glycoproteins in eliciting CTLs was assessed from the effectiveness of each of the virus mutants to stimulate the secondary anti-PrV CTL response. Cultures of both murine or swine lymphocytes that had been stimulated with gIII- virus contained only approximately half as many lytic units as did those stimulated with either wild-type virus, a gX- virus mutant, or a gI-/gp63- virus mutant. Thus, a large proportion of the PrV-specific CTLs that are induced by immunization with PrV of both mice and pigs are directed against gIII. Furthermore, glycoproteins gI, gp63, and gX play at most a minor role in the CTL response of these animals to PrV.

Animals↗
PubMed1988

Murine trophoblast resists cell-mediated lysis. II. Resistance to natural cell-mediated cytotoxicity.

The susceptibility of murine trophoblast cells to natural cell-mediated cytotoxicity has been assessed. Primary short-term cultures of murine trophoblast cells isolated from 14-day placentas were found to be resistant to endogenous and interferon-activated natural killer (NK) cells and natural cytotoxic cells. That the relevant target structures are expressed on the surface of trophoblast cells and accessible to the effectors was demonstrated by their ability to inhibit the lysis of NK-sensitive target cells (YAC-1) in a dose-dependent manner. The lytic resistance of trophoblast cells was unaffected by neuraminidase treatment, inhibition of protein synthesis, or extending the assay time to 12 hr. Moreover, trophoblast cells were resistant to antibody-dependent cell-mediated cytotoxicity when coated with an alloantibody capable of mediating their lysis in the presence of heterologous complement. Neither the preincubation of effector cells in concentrated trophoblast culture supernatants nor the direct exposure of effectors to monolayers of trophoblast cells inhibited their NK lytic activity, indicating that the secretion of a suppressive factor or the direct inactivation of the NK cells was not responsible for the observed resistance to lysis. These observations, together with previous results showing the resistance of trophoblast to cytotoxic T cell-mediated lysis, reveal that murine trophoblast cells possess a resistance mechanism against several forms of cell-mediated lysis. This feature of trophoblast cells at the maternal-fetal interface is likely to play an important role in protecting the fetoplacental allograft from immune rejection.

Animals↗
PubMed1988

Complex between glycoproteins gI and gp63 of pseudorabies virus: its effect on virus replication.

To ascertain the biological functions of different glycoproteins that are nonessential for pseudorabies virus growth in vitro, we have constructed mutants defective in one (or a combination) of these glycoproteins and have examined various aspects of their role in the infective process. We made the following two observations. (i) Glycoproteins gI and gp63 are noncovalently complexed to each other. They are coprecipitated by antisera against either one of these glycoproteins but do not share antigenic determinants: monoclonal antibodies against gp63 do not immunoprecipitate gI from extracts of gp63- mutant-infected cells, and monoclonal antibodies against gI do not immunoprecipitate gp63 from extracts of gI- mutant-infected cells. (ii) Mutants unable to synthesize either gI or gp63 have some common biological characteristics; they have a growth advantage in primary chicken embryo fibroblasts. Furthermore, we have shown previously that in conjunction with glycoprotein gIII, gI and gp63 are necessary for the expression of virulence (T. C. Mettenleiter, C. Schreurs, F. Zuckermann, T. Ben-Porat, and A. S. Kaplan, J. Virol. 62, 2712-2717, 1988). These results show that the functional entity affecting virus replication in chicken embryo fibroblasts, as well as affecting virulence, is the complex between gI and gp63. The gI-gp63 complex of pseudorabies virus does not appear to have Fc receptor activity as does its homolog, the gI-gE complex of herpes simplex virus.

Animals↗
PubMed1987

Murine trophoblast resists cell-mediated lysis. I. Resistance to allospecific cytotoxic T lymphocytes.

Research on the mechanisms of nonrejection of the fetoplacental allograft has focused on the tissues composing the fetomaternal interface, of which the placental trophoblast, the tissue directly confronting the maternal environment, is considered a prime candidate responsible for the survival of the fetus. We recently developed a method for isolating murine trophoblast, and found that a proportion of trophoblast cells from mature placentas, cultured for 2 days, express class I antigens on their surface, and this expression can be enhanced in vitro by interferon-alpha/beta (IFN-alpha/beta). In the present study, it was determined that cultured trophoblast cells from day 14 placentas were resistant to allospecific cytotoxic T lymphocytes (allo-CTL), while being susceptible to alloantibody and complement-mediated lysis. The trophoblast cells remained resistant to allo-CTL-mediated lysis despite IFN-mediated enhanced expression of class I H-2 antigens on their surface and the addition of phytohemagglutinin into the assay. Inhibition of protein synthesis also had no effect. In contrast, fetal fibroblasts, isolated from the same conceptuses, were readily susceptible to allo-CTL-mediated lysis. That the trophoblast cells do interact with the effector cells was shown by their ability to specifically inhibit the lysis of tumor target cells in a dose-dependent manner. Additionally, trophoblast culture supernatants did not inhibit the lytic activity of allo-CTL, even when concentrated 10- to 25-fold, indicating that a soluble suppressor factor was not inactivating the effector cells. These results suggest that trophoblast cells have a protein synthesis-independent mechanism of resistance to lysis by allo-CTL, which could play an important role in protecting the fetoplacental allograft from maternal immune rejection.

Animals↗
PubMed1987

Major histocompatibility antigens on trophoblast and their regulation: implications in the maternal-fetal relationship.

Recent technological advances have provided methods of detecting antigens encoded by the major histocompatibility complex with greater precision, allowing the expression of such antigens on the components of the placenta to be clarified. Of specific interest is the expression of these antigens on trophoblast cells, the fetal-derived epithelial cells that confront maternal blood and tissues at the maternal-fetal interface. It is now clear that the different trophoblast subpopulations differentially express class I antigens, although none appear to express class II antigens. Class I antigens can be induced by exposure to interferons on some populations but apparently not others, suggesting that the regulation of their expression differs for subpopulations of trophoblast cells, depending on gestational stage and location. This restricted expression has important implications for maternal-fetal immune interactions during the different phases of pregnancy and perhaps also bears on physiological functions of the feto-placental unit, such as growth and differentiation.

Animals↗
PubMed1986

Expression of MHC antigens on murine trophoblast and their modulation by interferon.

Primary cultures of defined populations of mouse trophoblast, isolated from mature placentas, were analyzed for their MHC antigen expression and for the modulatory effect of interferon (IFN) by antibody- and complement-mediated cytotoxicity and flow cytofluorometry. The cells were obtained from placentas by enzymatic digestion, followed by Percoll gradient fractionation, and are large, fetally derived epithelial cells, which we previously characterized and identified as trophoblast cells. After 2 days in culture, a significant proportion of the trophoblast cells were susceptible to antibody- and complement-mediated lysis by anti-paternal strain alloantisera (40%) and, to a lesser degree, by an anti-class I monoclonal antibody (20%). Flow cytofluorometric analysis indicated that 20 to 50% of the cultured trophoblast cells expressed low levels of paternal strain class I antigens as compared to L cell fibroblasts. After culture for 48 hr with IFN-alpha/beta or IFN-gamma, the percent of class I-positive cells was increased to 68 to 76%, as was the mean fluorescence intensity, which correlated with the increased percent of antibody- and complement-mediated specific lysis (73%). No expression of class II MHC antigen by the cultured trophoblast cells was detected, even after culture in the presence of IFN-gamma. The cultured trophoblast cells, when tested for alkaline phosphatase (AP) activity, were composed of strongly positive and weakly positive subpopulations. An inverse correlation between strength of AP activity and the expression of H-2 was observed by double staining. These results indicate that trophoblast cells cultured in vitro are able to express paternal strain class I but not class II MHC antigens, as has been reported in vivo, and that this expression can be modulated by IFN. Further study of these cells should provide important clues for the understanding of materno-fetal coexistence in the face of MHC antigen differences.

Alkaline Phosphatase↗
PubMedDate not supplied

Isolation and characterization of trophoblast from murine placenta.

A discontinuous density gradient centrifugation method, devised to isolate enriched populations of trophoblast from murine definitive placentae, is described. It is concluded that the isolated adherent cells are trophoblast on the basis of the following characteristics: they are fetally derived, as determined by their donor glucose phosphate isomerase phenotype in embryo transfer experiments; epithelial cells, as shown by the presence of cytokeratin filaments and the absence of vimentin; negative for the stage-specific embryonic antigen-I (SSEA-I); and capable of progesterone secretion. Initially, they grew as individual polygonal cells, tending to form tight confluent monolayers with poorly defined intercellular boundaries. They were mono- or binucleate and increased their nuclear size with time. After two days, giant cells appeared to be formed from binucleated cells by nuclear fusion, and multinucleated cells appeared forming syncytia. Some of these cells also seemed to form giant cells. A low percentage (1 to 10 per cent) of contaminating cells, mainly macrophage-like cells, was observed. The isolated cells were a mixture of alkaline phosphatase- (AP-)positive and AP-negative cells, with some of the latter having phagocytic capacity. All were Fc receptor-negative. The possible identity of these cells in relation to trophoblast in the intact placenta is discussed. This method of isolating and characterizing trophoblast cells from the definitive mouse placenta will be a useful tool for studying the biology and immunology of trophoblast.

Animals↗
PubMedDate not supplied

Aujeszky's disease virus: opportunities and challenges.

Since its description in 1902, Aujeszky's disease (AD) has become one of the most thoroughly examined viral diseases of swine. The causative agent, Aujeszky's disease virus (ADV), is a neurotropic alphaherpesvirus that produces fatal encephalitis in newborn pigs and a milder syndrome in older animals. In several instances this virus has been used as a test case to examine novel vaccine concepts in swine, including the honor of being the first genetically modified vaccine used in the field. Furthermore, the examination of the immune response to infection or vaccination with this virus has revealed important information about the function of the porcine immune system, including evidence on the existence of a dichotomy between the humoral and cellular immune response in swine. This review presents a summary of research where ADV has been a valuable tool for the development of novel vaccines and has provided information to better understand the immune response of swine to infectious agents.

Animals↗