The development and specificity of cytotoxic cells in cattle immunized with autologous or allogeneic<i>Theileria annulata–infected</i>lymphoblastoid cell lines

Innes, Elisabeth A.; Millar, P.G.; Brown, C.G.D.; Spooner, R. L.

doi:10.1111/j.1365-3024.1989.tb00648.x

Cited by 43 publications

(30 citation statements)

References 25 publications

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“…CTL are present in cattle infected with other intracellular pathogens, including viral (8), bacterial (27), and protozoal (9) agents. CTL are considered major antiparasite effectors in bovine theileriosis, for which the generation of CTL is closely related to control, and macroschizont-infected cells are killed in a major histocompatibility complex (MHC) class I-restricted manner (20). CTL are therefore expected to contribute to immune control of bovine N. caninum infections.…”

Section: Cd8mentioning

confidence: 99%

Neospora caninum-Infected Cattle Develop Parasite-Specific CD4⁺Cytotoxic T Lymphocytes

et al. 2003

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Cattle infected with Neospora caninum readily experience transplacental parasite transmission, presumably after maternal parasitemia, leading to abortion or birth of congenitally infected calves. Cytotoxic T lymphocytes (CTL) are important mediators of protective immunity against Toxoplasma gondii, an intracellular apicomplexan protozoan closely related to N. caninum. In this study, N. caninum-specific CTL expanded from peripheral blood mononuclear cells of two major histocompatibility complex-mismatched, experimentally infected cattle were identified by using a 51 Cr release cytotoxicity assay. Enrichment and blocking of CD4 ؉ -and CD8 ؉ -T-lymphocyte effector subsets indicated that CD4 ؉ CTL killed N. caninum-infected, autologous target cells and that killing was mediated through a perforin/granzyme pathway. Detection and characterization of CTL responses to N. caninum in the natural, outbred, bovine host will facilitate identification of immunogens and design of immunization strategies to induce parasite-specific CTL against transplacental N. caninum transmission in cattle.

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Section: Cd8mentioning

confidence: 99%

Neospora caninum-Infected Cattle Develop Parasite-Specific CD4⁺Cytotoxic T Lymphocytes

et al. 2003

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“…These studies revealed that schizont-containing cells stimulated autologous as well as allogeneic lymphocytes to proliferate and to produce cytokines. In addition, CTLs (Pearson et al 1979;Emery et al 1981;Eugui et al 1981;Preston et al 1983;Ahmed et al 1989a;Innes et al 1989) and helper T-cells (Baldwin et al 1987;Ahmed et al 1989b) were generated in peripheral blood mononuclear cells (PBMCs) of immune animals upon cultivation with macroschizont-infected cells.…”

Section: Cell-mediated Immune Responsementioning

confidence: 99%

Review: the cellular basis of the immunity to and immunopathogenesis of tropical theileriosis

Ahmed

Mehlhorn

1999

Parasitol Res

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The intracellular protozoan parasite Theileria annulata causes a severe and often fatal disease of pure and crossbred cattle in tropical and subtropical countries. Animals that recover from the infection are immune against challenge with homologous parasite strains. In the present review we refer to the role of immunocompetent cells and their products in containing the infection or in facilitating the progress of the disease. Parasite-infected host cells produce cytokines, which, depending on their concentration and timing of production, may enhance the establishment of the infection. Thus, cell lines producing high levels of proinflammatory cytokines cause severe postvaccinal reactions when inoculated into cattle. This may be supported by an aberrant non-specific activation of naive T-cells, leading to the production of high levels of gamma-interferon (IFN-y). Under these circumstances development of the specific immune response may be inhibited. At this stage, innate immune reactions are operating to contain the infection. Natural killer cells and macrophages may represent the most important part of this immunity. Antibodies and specific T-lymphocytes, CD4+ T-cells and cytotoxic T-lymphocytes (CTLs), play the most important role in a challenge infection. In this context, CD4+ T-cells produce cytokines required for the clonal expansion of CTLs that kill their target cells in a major histocompatibility complex (MHC) class I-restricted manner. In addition, CD4+ T-cells produce macrophage-activating cytokines such as IFN-gamma. Such activated macrophages produce mediators such as NO, which destroy the intracellular schizonts. Attempts have been directed toward the identification of parasite antigens involved in the induction of immunity. To date, only a limited number of sporozoite and merozoite antigens have been identified and examined for their immunogenicity, and the protection achieved is partial. An effective vaccine must include schizont proteins, notably, those proteins that are secreted into the host cell cytoplasm because these may have access to the MHC class I and II compartments to be presented to CTLs and CD4+ T-cells, respectively. Several schizont proteins have been identified and these are now under investigation.

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“…These biological features enable parasitized cells to be cultured in vitro as continuously growing cell lines (22). Despite the intimate relationship of the parasite with the host cell, inoculation of animals with a few thousand allogeneic T. annulata-infected cells results in transfer of infection into cells of recipient animals (24), by a mechanism that is poorly understood. This property has allowed parasitized cell lines to be used for vaccination, but such cell lines need to be subjected to prolonged passage in vitro followed by testing in vivo to ensure that they are fully attenuated for virulence (40,41).…”

mentioning

confidence: 99%

“…Cattle experimentally immunized with T. annulata-infected cell lines, generate strong parasite-specific CD8 T cell responses specific for the recipient animals' parasitized cells, coinciding with clearance of the immunizing infection (1,8,24,27,44). Given the evidence from studies of T. parva that such responses play a key role in immunity (33,34), antigens recognized by T. annulata-specific CD8 T cells represent potential candidates for the development of alternative vaccines.…”

mentioning

confidence: 99%

Extensive Polymorphism and Evidence of Immune Selection in a Highly Dominant Antigen Recognized by Bovine CD8 T Cells Specific for Theileria annulata

et al. 2011

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Although parasite strain-restricted CD8 T cell responses have been described for several protozoa, the precise role of antigenic variability in immunity is poorly understood. The tick-borne protozoan parasite Theileria annulata infects leukocytes and causes an acute, often fatal lymphoproliferative disease in cattle. Building on previous evidence of strain-restricted CD8 T cell responses to T. annulata, this study set out to identify and characterize the variability of the target antigens. Three antigens were identified by screening expressed parasite cDNAs with specific CD8 T cell lines. In cattle expressing the A10 class I major histocompatibility complex haplotype, A10-restricted CD8 T cell responses were shown to be focused entirely on a single dominant epitope in one of these antigens (Ta9). Sequencing of the Ta9 gene from field isolates of T. annulata demonstrated extensive sequence divergence, resulting in amino acid polymorphism within the A10-restricted epitope and a second A14-restricted epitope. Statistical analysis of the allelic sequences revealed evidence of positive selection for amino acid substitutions within the region encoding the CD8 T cell epitopes. Sequence differences in the A10-restricted epitope were shown to result in differential recognition by individual CD8 T cell clones, while clones also differed in their ability to recognize different alleles. Moreover, the representation of these clonal specificities within the responding CD8 T cell populations differed between animals. As well as providing an explanation for incomplete protection observed after heterologous parasite challenge of vaccinated cattle, these results have important implications for the choice of antigens for the development of novel subunit vaccines. CD8 T cells have been shown to play a key role in immunity to a variety of intracellular pathogens (65), including a number of protozoan parasites (33,36,38,55). A characteristic feature of CD8 T cell responses is that, in individual hosts, they are often directed against a few dominant epitopes (67). Consequently, mutations in sites encoding these epitopes can result in escape from immune recognition. This is well established as an important phenomenon in infections with some RNA viruses that exhibit a high rate of mutation, most notably, HIV-1 (18, 26, 39). Parasite strain-restricted CD8 T cell responses have also been reported for several protozoan infections, including human malaria and theileriosis in cattle (15,17,35). In the case of Theileria parva, variation between animals in the strain specificity of CD8 T cell responses has been shown to correlate with incomplete cross-protection between parasite strains (54). These observations suggest that polymorphism of the target parasite antigens may have arisen as a result of CD8 T cell imposed immune selection.The bovine tick-borne parasites Theileria parva and T. annulata infect and transform leukocytes, causing acute lymphoproliferative diseases that result in high levels of mortality and heavy production losses (25)....

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The development and specificity of cytotoxic cells in cattle immunized with autologous or allogeneicTheileria annulata–infectedlymphoblastoid cell lines

Cited by 43 publications

References 25 publications

Neospora caninum-Infected Cattle Develop Parasite-Specific CD4⁺Cytotoxic T Lymphocytes

Neospora caninum-Infected Cattle Develop Parasite-Specific CD4⁺Cytotoxic T Lymphocytes

Review: the cellular basis of the immunity to and immunopathogenesis of tropical theileriosis

Extensive Polymorphism and Evidence of Immune Selection in a Highly Dominant Antigen Recognized by Bovine CD8 T Cells Specific for Theileria annulata

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The development and specificity of cytotoxic cells in cattle immunized with autologous or allogeneicTheileria annulata–infectedlymphoblastoid cell lines

Cited by 43 publications

References 25 publications

Neospora caninum-Infected Cattle Develop Parasite-Specific CD4+Cytotoxic T Lymphocytes

Neospora caninum-Infected Cattle Develop Parasite-Specific CD4+Cytotoxic T Lymphocytes

Review: the cellular basis of the immunity to and immunopathogenesis of tropical theileriosis

Extensive Polymorphism and Evidence of Immune Selection in a Highly Dominant Antigen Recognized by Bovine CD8 T Cells Specific for Theileria annulata

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Neospora caninum-Infected Cattle Develop Parasite-Specific CD4⁺Cytotoxic T Lymphocytes

Neospora caninum-Infected Cattle Develop Parasite-Specific CD4⁺Cytotoxic T Lymphocytes