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Biomedical subjects

A J Teale

Publications and source records attributed to A J Teale.

At least 55 records · Page 3Linked to original sources
PubMed1989

Biochemical characterization of activation-associated bovine class I major histocompatibility complex antigens.

Utilizing a 'sandwich' ELISA assay we have been able to demonstrate that mAb W6/32, B1G6 and IL-A19 are reactive with three different monomorphic determinants on bovine class I major histocompatibility complex (MHC) molecules. Sequential immunoprecipitations performed with the mAb revealed that class I molecules on PBM comprise a single population with respect to reactivity with the mAb in that the beta 2m-associated proteins bear all three epitopes. By contrast, TCGF-driven lymphoblasts and cells transformed by Theileria parva (Tp) additionally express molecules of Mr 45000 bound to beta 2m which are recognized by mAb B1G6 and IL-A19 but not by W6/32. These two subclasses of molecules were further distinguished on the basis that, when tunicamycin was added to cultures in the preparation of cells for analysis, mAb W6/32 precipitated class I heavy chains of Mr 39000 while the extra molecules detected only by mAb B1G6 and IL-A19 were of Mr 37000 and 39000. On thymocytes, the mAb W6/32-non-reactive class I molecules are present in low amounts and are expressed by cells in the medulla area, unlike BoT1 (analogous to human CD1) molecules which are expressed by the cortical cells. Our studies also revealed that the supposed beta 2m-specific mAb B1G6 does not recognize the beta 2m-associated molecules (BoT1) precipitated by mAb TH97A and thus the specificity of mAb B1G6 in cattle is for an epitope on bovine beta 2m which is strongly influenced by the nature of the heavy chain with which the beta 2m is associated.

Animals↗
PubMed1989

Trypanotolerance and the value of conserving livestock genetic resources.

Studies have been made in two main areas of genetic research on African trypanotolerant (N'Dama) cattle. The first is of the significance for performance and the heritability of trypanotolerance traits and the second is the search for markers of the breed type and the traits of interest. Results demonstrate significant effects of the ability of an animal to control parasitaemia and anaemia on its performance. Initial estimates suggested that parasitaemia measures had a very low heritability, but ability to maintain packed cell volume levels when detected as parasitaemic and to generate an immune response could form the basis of a practical selection approach. The search for markers has so far concentrated on the major histocompatibility complex and on a polymorphic system of common leukocyte antigens. Phenotypes that appeared more characteristic of the N'Dama in comparison with those of East African zebu cattle were examined for associations with trypanotolerance traits. One major histocompatibility complex encoded phenotype and two common leukocyte antigens gave indications of important associations. Planned research will further characterise the breed and define traits of importance to assist in increasing its productivity in Africa and thus in its conservation. The addition of a molecular genetics component to an integrated genetics research programme, principally through involvement in development of a linkage map of the bovine genome, will strengthen these efforts and make it possible to conserve specific N'Dama genes related to productivity.

Africa↗
PubMed1989

[The major histocompatibility complex of West African cattle. Typing of lymphocyte antigens (BoLA) of Baoulé cattle (Bos taurus) and Sudanese zebus (Bos indicus) of Burkina Faso (West Africa)].

Lymphocyte antigen (BoLA) typing on 247 Baoule cattle (Bos taurus) and 106 Sudanese zebus (Bos indicus), allowed us to determine gene frequencies of 43 class 1 specificities, as international "W" and European "EU", as African local from Kenya "KN" and Burkina Faso "BF". In comparing these frequencies, it appears that some specificities could be considered as significant breed markers for Baoule cattle and zebus.

Animals↗
PubMed1988

A comparative study of major histocompatibility complex antigens in east African and European cattle breeds.

An account is given of the serologically defined class I specificities encoded by the bovine MHC (expressed as the BoLA system) in two populations of African cattle and in European breeds. The BoLA typing was performed using alloantisera raised against tissue antigens of both European and African breeds of cattle. All of the specificities agreed in the first two international BoLA workshops were found in the African cattle, although there were significant differences in the frequency of some specificities between the African and European animals. Many of the European antisera, which are operationally monospecific in Bos taurus cattle, were multispecific in the African animals. Subgroups of two specificities (w8 and w10) were demonstrated. Five new BoLA-A locus alleles were detected by means of antisera raised against alloantigens of African cattle. Two of these occurred at an extremely high frequency in the African populations; one being unique to these cattle. Monoclonal antibodies proved to be useful typing reagents, particularly in the elucidation of subgroups.

Africa, Eastern↗
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

Alloreactive T cell clones transformed by Theileria parva retain cytolytic activity and antigen specificity.

Theileria parva is a protozoan parasite which infects and transforms bovine lymphocytes. This study examined the effects of Theileria-induced transformation on phenotype and function, in terms of cytolytic potency and specificity, of class I and class II-specific alloreactive T cell clones. Alloreactive T cell clones infected with T. parva (Muguga) retained expression of the T cell differentiation antigens BoT2, BoT4, BoT8 and the mature T cell antigen recognized by monoclonal antibody IL-A27, as well as cytolytic function and antigen specificity, over a period of 3-4 months in continuous culture. These features were identical to those expressed by the uninfected parent clones. During this period, neither antigenic stimulation nor exogenous growth factors were required for the maintenance of proliferation, function or antigen specificity. Thereafter, cytolytic activity declined and was eventually lost, which may reflect degenerative changes normally associated with T cell senescence rather than result from parasitization per se.

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↗
PubMed1987

A study of BoLA class II antigens with BoT4+ T lymphocyte clones.

It has hitherto proved difficult to phenotype cattle for class II histocompatibility antigens using standard serological techniques because of problems of reagent specificity and antigen expression on peripheral blood mononuclear cells (PBMs). We recently described the production of class II-specific alloreactive bovine T cell clones characterized by the BoT4+ phenotype. In this report we describe studies of the application of four such clones, derived from a single mixed leucocyte culture (MLC), for class II phenotyping in proliferation and cytotoxicity assay systems. Proliferation assays used irradiated PBM as stimulator cells and cytotoxicity assays used Theileria parva-infected lymphoblastoid cells as targets. Proliferation assays revealed three distinct specificities among the four clones indicating that they detected three different class II determinants. Furthermore, in a family study, the genes encoding the determinants recognized by the clones were found to be linked to the gene encoding the w10 class I A locus product on one of the w10-bearing haplotypes in our study population. Two of the clones were studied in cytolysis assays. Lack of cytolysis of one of the targets, which was derived from the PBM of an animal carrying a class II determinant detected in proliferation assay, was explained by the total lack of expression of class II antigens on the target cell line in question, as determined with 4 class II-specific monoclonal antibodies (mAb). We conclude that BoT4+ alloreactive clones provide a potentially useful and particularly discriminating way of detecting polymorphic class II antigens of cattle, especially when applied in assays of proliferative response to PBM.

Animals↗
PubMed1987

Cytotoxic T-cells elicited in cattle challenged with Theileria parva (Muguga): evidence for restriction by class I MHC determinants and parasite strain specificity.

The MHC restriction and parasite strain specificity of cytotoxic cells elicited in a group of Theileria parva (Muguga)-immunized cattle following homologous challenge, were investigated. The cytotoxic cells were specific for parasitized target cells and in 9 of the 10 animals examined, they were clearly genetically restricted. Cytotoxicity could be inhibited by monoclonal antibodies (MoAb) to class I MHC molecules but not by MoAb to class II molecules, indicating that a large component of the response was restricted by class I MHC determinants. Low levels of inhibition of cytotoxicity were also obtained with a MoAb to the T-cell subset marker BoT8, suggesting that at least part of the response was mediated by BoT8+ lymphocytes. When cytotoxic cells from individual cattle were assayed on panels of parasitized target cells, there was a close correlation between susceptibility of the target cells to lysis and sharing of BoLA-A locus-encoded specificities with the effectors. This observation, taken together with the knowledge that within several of the sets of BoLA-A-matched targets the relevant BoLA-A specificities were on different MHC haplotypes, indicated that the responses were restricted predominantly by BoLA-A products. In individual cattle there was a striking bias in the restriction of the response to one or other BoLA-A specificity. Among the six specificities represented, responses restricted by w6, w8 and KN18 consistently predominated over responses restricted by w7, w10 and w11. In the three cattle tested for parasite strain specificity, two showed complete specificity and one partial specificity for cells infected with the parasite stock used for immunization, T. parva (Muguga).

Animals↗
PubMed1987

Bovine alloreactive cytotoxic cells generated in vitro detect BoLA w6 subgroups.

Alloreactive cytotoxic T cells (CTL) were generated in mixed lymphocyte culture against cells bearing subgroups of BoLA w6, as well as in BoLA w4, w10 and w16. Primary cultures were restimulated at weekly intervals with irradiated stimulator cells and tested in a 51Cr-release assay with target cells derived from Theileria annulata-infected cell lines. Generation of CTL was accelerated in animals that had been previously primed in vivo by skin grafting. CTL were generated that were specific for BoLA w6 subgroups and not w6. With w6.1 the specific killing was significant at the 5% level, and with w6.2, 6.3 and 6.4 it was significant at the 0.1% level. Where CTL were potentially generated against two BoLA-A locus allele products at the same time (i.e. with heterozygous stimulator cells), one of which was a w6 subgroup, there was similar CTL activity against both products when w6.4 and w16 or w6.1 and w4 were the combinations involved. In two generations against w10 and either w6.1 or w6.2 there was significantly more killing of w10-bearing targets than those with the w6 subgroup.

Animals↗
PubMed1986

Characterization of a subset of bovine T lymphocytes that express BoT4 by monoclonal antibodies and function: similarity to lymphocytes defined by human T4 and murine L3T4.

We report the identification of a subset of bovine T cells by two monoclonal antibodies (mAb), IL-A11 and IL-A12, and some functional analyses of these cells. Both mAb precipitate two polypeptides, called BoT4, with apparent molecular mass of 52 and 55 kilodaltons. The epitopes recognized by these two mAb are different, however. BoT4 is found on approximately 70% of thymocytes and 30% of peripheral blood mononuclear cells (PBM), is not expressed by monocytes or B cells, and is found on cells in the T-dependent areas of lymph nodes. BoT4+ lymphocytes purified by a fluorescence-activated cell sorter proliferate in response to mitogenic and alloantigenic stimulation without addition of exogenous growth factors, whereas BoT4- lymphocytes do not. Monoclonal antibodies IL-A11 and IL-A12 have no effect on mitogen- (PHA and Con A) or alloantigen-induced proliferation of PBM. Monoclonal antibody IL-A12 has no inhibitory effect on the cytolytic activity of bulk populations of alloreactive T lymphocytes, and most of the cytolytic activity generated in mixed leukocyte culture is ascribable to the BoT4- population. Using cloned alloantigen-specific lymphocytes, we found that the ability of BoT4+ clones to proliferate to alloantigenic stimuli without exogenous growth factors is a characteristic of some clones, as is susceptibility to inhibition of proliferation by mAb IL-A12. These results implicate the BoT4 molecule in antigen recognition but indicate that the requirement for BoT4 is variable among clones. Our findings, together with those in the companion paper, which provides evidence that BoT4+ lymphocytes are class II restricted, indicate that BoT4+ lymphocytes are the bovine equivalent of Leu3/T4+ lymphocytes of humans and analogous lymphocytes of other species.

Animals↗
PubMed1986

Alloreactive bovine T lymphocyte clones: an analysis of function, phenotype, and specificity.

A bovine alloreactive cell population was subjected to complement-dependent lysis with monoclonal antibody (mAb) IL-A11. The original population and the population depleted of cells bearing the determinant recognized by mAb IL-A11 were cloned. Parent cultures and 21 clones were examined for cytolytic function and for expression of determinants recognized by mAb IL-A11 and two additional mAb, IL-A12 and IL-A17. Clones could be classified according to maximal achievable levels of cytolysis by using Theileria parva-infected bovine lymphoblastoid target cells. In this way, three groups were identified--one capable of high level cytolysis, one of intermediate levels, and one group comprising apparently noncytolytic clones. The clones in the first group reacted with mAb IL-A17; those in the second and third groups, with mAb IL-A11 and IL-A12. It was shown that cytotoxicity effected by IL-A17+ clones could be inhibited by this mAb and also by a mAb directed to MHC class I determinants on target cells. Conversely, cytotoxicity effected by IL-A11+/IL-A12+ clones could be inhibited by mAb IL-A11 and by a mAb directed to MHC class II determinants on target cells. The levels of expression of class I and class II determinants on target cells correlated with the levels of killing by clones of the IL-A17+ phenotype and clones of the IL-A11+/IL-A12+ phenotype, respectively. The results indicate that cytotoxic bovine T lymphocyte clones specific for class I MHC antigens and both cytotoxic and noncytotoxic clones specific for class II MHC antigens can be obtained. Further, their specificity for class I or class II antigens can be determined by phenotyping with mAb.

Animals↗
PubMed1986

Generation of bovine cytotoxic cell lines, specific for cells infected with the protozoan parasite Theileria parva and restricted by products of the major histocompatibility complex.

Cytotoxic cell lines specific for cells infected with the protozoan parasite Theileria parva were generated in vitro by repeated stimulation of peripheral blood mononuclear cells (PBMC) from immune animals with autologous parasitized cells from continuously growing cell lines. In PBMC of 5/7 immune animals tested, maximal levels of killing (80-100%) were obtained at effector to target ratios of 10/1 following 3 to 5 stimulations. No killing of uninfected lymphoblasts was observed. Cytotoxic activity was contained in the BoT4- lymphocyte population. The results of analyses of cytotoxicity on panels of target cells of diverse major histocompatibility (MHC) phenotypes indicated that the effectors were restricted by class I MHC antigens. Only autologous targets and allogenic targets sharing one or other bovine lymphocyte antigen A locus-encoded specificity with the cytotoxic cell line were killed. In addition, two of the three cytotoxic cell lines, when tested on targets infected with different parasite stocks, exhibited a high degree of specificity for the stock used for immunization and stimulation of the cultures. The capacity to generate highly cytotoxic, MHC-restricted effectors from peripheral blood was dependent on the immune status of the donor animals. This was confirmed by comparing cytotoxicity generated from the same animal before and after immunization using the same autologous infected cell line as a stimulator. These results indicate that these effector cells are analogous to the cytotoxic cells detected in vivo in cattle undergoing immunization or challenge with T. parva.

Animals↗