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W I Morrison

Publications and source records attributed to W I Morrison.

At least 73 records · Page 4Linked to original sources
PubMed1990

Identification of a bovine surface antigen uniquely expressed on CD4-CD8- T cell receptor gamma/delta+ T lymphocytes.

In this study, two monoclonal antibodies, IL-A29 and CC15, are described that identify a novel bovine cell surface marker of 215/300 kDa. The antibodies reacted with a discrete population of resting lymphocytes in peripheral blood which, in young animals, constituted about 25% of the mononuclear cells. Thymus, lymph nodes and spleen contained less than 5% positive cells. These cells were negative for surface Ig, a monocyte/granulocyte marker, and the T lymphocyte antigens CD2, CD6, CD4 and CD8. Immunohistological analyses revealed the presence of IL-A29/CC15-positive lymphocytes in the thymic medulla, in the outer cortex of lymph nodes, in the marginal zones of the spleen, in the dermal and epidermal layers of the skin and in the lamina propria of the gut. The IL-A29/CC15+ cells in unfractionated blood mononuclear cells responded in autologous and allogeneic mixed lymphocyte cultures, and when purified they responded to concanavalin A in the presence of recombinant interleukin 2. These observations suggested this population of cells belonged to the T cell lineage. In order to unambiguously define their lineage, cDNA clones encoding bovine T cell receptor (TcR) and CD3 proteins were isolated. Northern blot analyses of IL-A29/CC15+ cell populations and of established cell lines of various lineages demonstrated that they expressed TcR delta and CD3 gamma, delta and epsilon mRNA: TcR alpha was not expressed, whereas only a truncated form of TcR beta mRNA was present. These results indicate that the IL-A29 and CC15 antibodies define a unique population of CD4-CD8-, gamma/delta T cells.

Animals↗
PubMed1990

Theileria parva: the nature of the immune response and its significance for immunoprophylaxis.

Theileria parva is a tick-borne haemoprotozoan parasite of cattle and buffalo which is responsible for considerable economic losses to cattle farming in Eastern, Central and Southern Africa. Infection with the parasite results in an acute lymphoproliferative disorder with high mortality, but animals which survive infection are solidly immune to homologous challenge. Such immunity can be reproduced by infecting cattle with the parasite and treating them with tetracyclines or theilericidal drugs, but the widespread use of this technique as a method of control is hindered by its dependence on live parasites which require cryopreservation for maintenance and can give rise to carrier states. In addition, cross-protection between different strains of the parasite is not absolute. These problems have prompted a search for methods of immunisation based on the use of inactivated parasites or their derivatives. Such efforts have met with consistent failure, however, and in recent years scientists have adopted the more rational approach of defining the immune responses of cattle to the parasite with a view to identifying the parasite components which provoke them. These studies have revealed that protection is likely to be mediated by parasite-specific cytotoxic T cells which are restricted by class I major histocompatibility complex (MHC) products. The significance of this observation to the development of an effective subunit vaccine is discussed in the light of current knowledge of the inductive requirements of cytotoxic T cells.

Animals↗
PubMed1990

Strain specificity of bovine Theileria parva-specific cytotoxic T cells is determined by the phenotype of the restricting class I MHC.

To determine whether the major histocompatibility complex (MHC) phenotype of cattle could affect the parasite strain specificity of immunity to Theileria parva by influencing the antigenic specificity of Theileria-specific cytotoxic T lymphocytes (CTL), we investigated the parasite strain specificity of Theileria-specific CTL clones derived from cattle of different class I MHC phenotypes. Thirty-one class I-restricted CTL clones were generated from four cattle immunized with the Muguga stock of T. parva. The MHC restriction and parasite strain specificities were determined for each clone utilizing as targets, parasitized cell lines of different MHC phenotypes and cloned cell lines containing different parasite strains. CTL clones restricted by the same MHC determinant had similar parasite strain specificities. On the other hand, clones restricted by different MHC determinants exhibited different parasite strain specificities. This was true whether the clones were generated from the same animal or from different cattle and tested on a target cell line expressing both MHC determinants. These results provide strong evidence that differences in the strain specificities of CTL derived from animals immunized with the same parasite stock, are determined by the class I MHC phenotype of the immunized animal.

Animals↗
PubMed1990

Transfection into mouse L cells of genes encoding two serologically and functionally distinct bovine class I MHC molecules from a MHC-homozygous animal: evidence for a second class I locus in cattle.

w10 and KN104 are distinct class I major histocompatibility complex (MHC) serological specificities present in Boran (Bos indicus) cattle. Although these specificities are commonly expressed together, they may also be expressed independently. To establish whether w10 and KN104, when expressed together, are on the same or different molecules, and whether a second class I MHC locus exists in cattle, genomic DNA from an animal homozygous for a haplotype encoding the w10 and KN104 specificities was transfected into thymidine kinase-deficient mouse L cells (Ltk- cells), and the transfected cells were screened with monoclonal antibodies (mAb) specific for the w10 or KN104 allospecificities. Two different populations of transfectants were identified: the cells of one population reacted only with w10-specific mAb, whereas those of the other population were recognized only by the KN104-specific mAb. Alloreactive cytotoxic T lymphocytes (CTL) also distinguished between the two populations. Two CTL clones, shown to be restricted by the KN104 specificity, killed only those L cells expressing molecules recognized by the KN104-reactive mAb. Of eight CTL clones which recognized class I molecules associated with the w10 specificity, four killed the L cells expressing the w10 specificity. The remaining four clones did not kill either population of transfectants. Finally, immunoprecipitation studies revealed that both populations express full-length bovine class I MHC molecules. These results demonstrate that the w10 and KN104 specificities are on distinct class I molecules. As the genes encoding these molecules were derived from a MHC-homozygous animal, the findings also provide strong evidence that there are at least two classical class I loci in cattle.

Animals↗
PubMed1989

Demonstration of two allelic forms of the bovine T cell antigen Bo5 (CD5) and studies of their inheritance.

Two monoclonal antibodies (mAbs), CC17 and IL-A67, which are specific for the bovine equivalent of the CD5 antigen, Bo5, were each found to react with the cells of some animals but not others. The cattle tested were all positive for one or both of the mAbs, but the level of expression on cells expressing both determinants was slightly lower than that on cells expressing either of the determinants on their own. Both mAbs precipitated an antigen of 67 kD. However, sequential immunoprecipitation experiments with cells that reacted with both mAbs demonstrated that the determinants are present on two different sets of molecules. These findings suggested that the mAbs recognize two co-dominantly expressed allelic forms of Bo5. This was confirmed in family studies, with groups of full- and half-sibling offspring of sires and dams of defined phenotypes. These experiments also showed that the gene encoding the Bo5 antigen is not linked to the major histocompatibility complex (MHC). The frequencies of the two alleles, which have been designated Bo5.1 and Bo5.2, in the cattle populations tested were 100% and 0%, respectively, in Bos taurus, and 10% and 90%, respectively, in Bos indicus.

Alleles↗
PubMed1988

Differentiation antigens on bovine mononuclear phagocytes identified by monoclonal antibodies.

Five monoclonal antibodies (MAb) produced against cell surface antigens on bovine mononuclear phagocytes (MPh) were characterized. None of the MAb recognized erythrocytes, thrombocytes, B lymphocytes or resting or activated T lymphocytes. Two MAb (IL-A22 and IL-A24) reacted with the majority of monocytes and granulocytes in peripheral blood, with 20-40% bone marrow cells comprising myelo-monocytic cells, and with a proportion of mature macrophages. Reactivity of the remaining three MAb was restricted to MPh: one of these (IL-A25) was apparently specific for pulmonary macrophages, whereas the molecules recognized by the other two (IL-A23 and CH16A) were expressed on subpopulations of blood monocytes and tissue macrophages. None of the MAb inhibited adherence of MPh to plasma-coated gelating surfaces or Fc-mediated rosette formation. One of the MAb, IL-A24, which reacts with MPh and granulocytes, inhibited antigen-specific proliferative response or peripheral blood mononuclear leukocytes (PBM) to the soluble antigen, keyhole limpet hemocyanin (KLH) but did not inhibit responses to concanavalin A or allogeneic leukocytes. This MAb was shown to react with two polypeptides of approximately 75 kD and 110 kD on the surface of peripheral blood monocytes.

Animals↗
PubMed1988

T-cell clones in immunoparasitology.

Cell-mediated immunity (CMI) is important in many parasitic infections. Stimulation by parasite-specific antigens can induce clonal expansion of parasite-specific T-cells which may act by direct cytotoxic action or by indirect effects on other cells such as natural killer cells or antibody-producing B-cells (Box 1). In many cases however, the precise effector functions and the identity of antigens that elicit protective responses in parasitic infections are poorly defined. Analysis of proliferative and cytotoxic activities of subcloned cultures of T-cells stimulated with parasite antigens can provide some clues about the importance of CMI, but, as this review shows, much more precise information can be obtained by analysis of the response of cloned T-cell cultures.

Journal Article↗
PubMed1988

Theileria parva (Muguga) infects bovine T-lymphocytes in vivo and induces coexpression of BoT4 and BoT8.

During the course of a lethal infection with Theileria parva (Muguga), the surface phenotypes of efferent lymphatic lymphocytes (ELL) were analysed to determine whether the parasite preferentially infected any particular subpopulation of cells. In the second week of infection, when the proportion of lymphoblasts and parasitized cells increased to 50% of the total ELL, greater than 99% of infected cells expressed T-lymphocyte markers including both BoT4 and BoT8. From day 10, a population of T-lymphocytes coexpressing BoT4 and BoT8 appeared in ELL, reaching 33% by day 14. Similar changes were observed in peripheral blood mononuclear cells (PBM) and lymph node cells (LNC). Analysis of ELL sorted into populations differing on the basis of expression of BoT4 and BoT8, revealed a higher level of parasitosis in the BoT4+ and BoT8+ lymphocytes than in the BoT4+ BoT8- or BoT4- BoT8+ populations. For comparison, the phenotypes of 28 cloned cell lines, obtained by infection of PBM with sporozoites in vitro, were examined. All of these clones exhibited T-cell markers. Nine of the clones expressed both BoT4 and BoT8; within each of these lines, BoT4 was expressed on all cells, whereas BoT8 was expressed at variable concentrations on 20-70% of cells. That BoT4+ cells were induced by T.parva (Muguga) to coexpress BoT8 was demonstrated directly by the finding that a BoT4+ BoT8- T-cell clone expressed BoT8 following infection with the parasite.

Animals↗
PubMed1988

Bovine T cells, B cells, and null cells are transformed by the protozoan parasite Theileria parva.

The target cells for infection and transformation by Theileria parva were investigated. Peripheral blood mononuclear cells were reacted with monoclonal antibodies specific for bovine leukocyte differentiation antigens, sorted into subpopulations with a fluorescence-activated cell sorter, and infected in vitro with T. parva sporozoites. Infected cells were cultured at limiting dilution, and transformed clones were screened with monoclonal antibodies. The results indicated that B cells, T cells (including BoT4+ and BoT8+ cells), and null cells but not monocytes or neutrophils were transformed in vitro after infection with T. parva. After transformation, peripheral blood T cells and T-cell clones retained expression of most or all of the T-cell differentiation antigens including the mature T-cell marker recognized by monoclonal antibody IL-A27, BoT2, and BoT4 or BoT8, and some cells acquired a low level of expression of BoT4, BoT8, or the null cell marker recognized by monoclonal antibody IL-A29. T. parva-transformed null cells retained expression of the IL-A29 determinant and acquired expression of BoT2 and BoT8 but not the IL-A27 determinant or BoT4. T. parva-transformed B cells in most instances lost expression of surface immunoglobulin and never acquired expression of the IL-A27 determinant, BoT2, BoT4, or BoT8, although some cells acquired a low level of expression of the null cell marker recognized by monoclonal antibody IL-A29. Further studies on cell lines and clones grown in vitro from populations isolated from T. parva-infected cattle suggested that the majority of the in vivo T. parva-transformed cells were of T-cell origin.

Animals↗
PubMed1988

Monoclonal antibodies which react with bovine T-lymphocyte antigens and induce blastogenesis: tissue distribution and functional characteristics of the target antigens.

In this study we report on the tissue distribution and functional characteristics of bovine T-cell differentiation antigens recognized by the monoclonal antibodies (mAbs) IL-A26, IL-A27, and IL-A28. All three mAbs are able to stimulate proliferation of peripheral blood mononuclear cells (PBM) and inhibit proliferation of responder cells in mixed leucocyte cultures (MLC). MAbs IL-A27 and IL-A28 are believed to react with the same molecule, which is different to that recognized by IL-A26 as determined by a number of criteria. MAbs IL-A27 and IL-A28 inhibit binding of one another, but not of IL-A26. MAbs IL-A27 and IL-A28 react with 25% of thymocytes confined to the medulla, whereas IL-A26 reacts with approximately 80% of thymocytes, including medullary and cortical populations. MAbs IL-A27 and IL-A28 react with thymocytes which express BoT4 or BoT8 singularly, whereas IL-A26 reacts with all cells which express BoT4 or BoT8, either singularly or dually, in addition to all thymocytes which react with IL-A27/28. Only IL-A26 inhibits spontaneous sheep erythrocyte (E)-rosette formation by bovine T cells. Based on tissue distribution and functional characteristics, IL-A26 is believed to recognize the bovine homologue of CD2, designated BoT2, whereas IL-A27/28 reacts with a mature T-cell antigen. Cells reactive with the mAbs constitute approximately 60% of bovine PBM. Using these mAbs in dual immunofluorescence analyses, at least three populations of bovine T cells are demonstrable in PBM. The majority of T cells are BoT4+ or BoT8+ and also react with IL-A26/27/28. A second small population of PBM is negative for BoT4 and BoT8 but is IL-A26/27/28+. A third population (less than 5%) is BoT4-/BoT8-/ILA27/28- but reacts with IL-A26.

Animals↗
PubMed1987

Bovine cytotoxic T cell clones which recognize lymphoblasts infected with two antigenically different stocks of the protozoan parasite Theileria parva.

The Muguga and Marikebuni stocks of Theileria parva differ on the basis of cross-protection and in their schizont antigen profile determined with a panel of parasite-specific monoclonal antibodies. The phenotype and specificity of six cytotoxic T cell clones generated from an animal immunized against T. parva (Marikebuni) were investigated. All six clones had the BoT2+ BoT4- BoT8+ phenotype, were dependent on both specific antigen and T cell growth factor for proliferation and were restricted by determinants on class I major histocompatibility complex molecules. The clones killed target cells infected with either the Muguga or Marikebuni stocks of the parasite; the target cell lines tested included T cell clones which were infected in vitro with the two parasite stocks and subsequently recloned. The specificity of these cytotoxic T cell clones contrasts with that of T cell clones generated previously from animals immunized against T. parva (Muguga), in that the latter were specific for target cells infected with the Muguga stock of the parasite. Moreover, one of the clones generated against T. parva (Marikebuni) was restricted by the same major histocompatibility complex molecule as the Muguga-specific T cell clones. The difference in parasite strain-specificity between the two sets of clones appears to reflect the capacities of the two parasite stocks to cross-protect, since animals immunized against T. parva (Marikebuni) are protected against challenge with T. parva (Muguga) whereas a proportion of animals immunized with T. parva (Muguga) are susceptible to challenge with T. parva (Marikebuni). Another difference between the two sets of T cell clones was that those generated against T. parva (Marikebuni) only killed a proportion of cells of a given cell line in a 4-h cytotoxicity assay, whereas Muguga-specific T cells invariably kill the majority of cells. However, despite this partial killing, the clones markedly inhibited growth of parasitized cell lines when cultured with them for a period of 5 days.

Animals↗
PubMed1987

Phenotypic and functional characteristics of bovine T lymphocytes.

Monoclonal antibodies have been derived which detect the bovine equivalents of the human pan-T cell marker CD2 and the T lymphocyte subpopulation markers CD4 and CD8. We refer to the bovine analogues as BoT2, BoT4 and BoT8. Monoclonal antibodies have also been derived which detect an antigen(s) with similarities to CD3, although the precise nature of the target molecule(s) in this instance remains to be elucidated. In general there is close similarity between the tissue distributions and, where these have been determined, the molecular masses of the BoT2, BoT4, BoT8 and putative BoT3 entities and their counterparts in other species. BoT2 is expressed on a majority of peripheral blood T lymphocytes and thymocytes and BoT2+ cells are found in both thymic cortex and medulla. In contrast, the putative BoT3 marker is expressed by a minority of thymocytes which are moreover, largely restricted to medulla. Monoclonal antibodies detecting BoT2 determinants have been shown to precipitate 55 kDa molecules. Antibodies to the BoT2 and BoT3 entities have been shown to induce proliferation in peripheral blood mononuclear cells of some cattle, and to be capable of inhibition of antigen-driven proliferative responses and cytolytic function. The BoT4 and BoT8 markers are expressed in a mutually exclusive manner by bovine peripheral blood mononuclear cells but they are coexpressed on a large population of thymocytes. Monoclonal antibodies have been used to precipitate molecules of 52 and 55 kDa in the case of those detecting BoT4 and 34 and 35 kDa in the case of an antibody reactive with a BoT8 determinant. The BoT4 and BoT8 markers have been associated with specificity for, and restriction by, MHC class II and class I molecules respectively.

Animals↗