Theileria parva: Kinetics of infection in the lymphoid system of cattle

Morrison, W. Ivan; Büscher, G.; Murray, M.; Emery, D.L.; Masake, R.A.; Cook, R. H.; Wells, P.W.

doi:10.1016/0014-4894(81)90080-1

Cited by 52 publications

(29 citation statements)

References 8 publications

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“…Increased resistance to Fas-induced apoptosis might also contribute to the pathogenesis of East Coast fever. Theileria-transformed cells have been shown to induce a pronounced autologous mixed lymphocyte reaction in vitro (50,51), a process that, in vivo, is thought to contribute to the accumulation of large numbers of uninfected lymphoblastoid cells in the animal's lymphoid tissues (52,53). As it can be expected that Fas and FasL are up-regulated as a consequence of this activation, enhanced resistance against Fas-induced apoptosis might impart a selective advantage to parasitized cells over uninfected cells, thus contributing to the clonal expansion and spread of the infected cells through the body.…”

Section: Discussionmentioning

confidence: 99%

“…As it can be expected that Fas and FasL are up-regulated as a consequence of this activation, enhanced resistance against Fas-induced apoptosis might impart a selective advantage to parasitized cells over uninfected cells, thus contributing to the clonal expansion and spread of the infected cells through the body. East Coast fever is characterized by an initial phase of lymphoproliferation, which is usually followed by massive lymphocytolysis involving uninfected as well as T. parva-infected cells (53). At this stage, the molecular basis for this lytic response is not known, but it will be of interest to determine to what extent Fas/ FasL expression plays a role in this process.…”

Section: Discussionmentioning

confidence: 99%

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Theileria parva-Transformed T Cells Show Enhanced Resistance to Fas/Fas Ligand-Induced Apoptosis

Küenzi

Schneider

Dobbelaere

2003

The Journal of Immunology

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Lymphocyte homeostasis is regulated by mechanisms that control lymphocyte proliferation and apoptosis. Activation-induced cell death is mediated by the expression of death ligands and receptors, which, when triggered, activate an apoptotic cascade. Bovine T cells transformed by the intracellular parasite Theileria parva proliferate in an uncontrolled manner and undergo clonal expansion. They constitutively express the death receptor Fas and its ligand, FasL but do not undergo apoptosis. Upon elimination of the parasite from the host cell by treatment with a theilericidal drug, cells become increasingly sensitive to Fas/FasL-induced apoptosis. In normal T cells, the sensitivity to death receptor killing is regulated by specific inhibitor proteins. We found that anti-apoptotic proteins such as cellular (c)-FLIP, which functions as a catalytically inactive form of caspase-8, and X-chromosome-linked inhibitor of apoptosis protein (IAP) as well as c-IAP, which can block downstream executioner caspases, are constitutively expressed in T. parva-transformed T cells. Expression of these proteins is rapidly down-regulated upon parasite elimination. Antiapoptotic proteins of the Bcl-2 family such as Bcl-2 and Bcl-xL are also expressed but, in contrast to c-FLIP, c-IAP, and X-chromosome-linked IAP, do not appear to be tightly regulated by the presence of the parasite. Finally, we show that, in contrast to the situation in tumor cells, the phosphoinositide 3-kinase/Akt pathway is not essential for c-FLIP expression. Our findings indicate that by inducing the expression of antiapoptotic proteins, T. parva allows the host cell to escape destruction by homeostatic mechanisms that would normally be activated to limit the continuous expansion of a T cell population.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Theileria parva-Transformed T Cells Show Enhanced Resistance to Fas/Fas Ligand-Induced Apoptosis

Küenzi

Schneider

Dobbelaere

2003

The Journal of Immunology

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“…T. parva is a protozoal pathogen of cattle that replicates in the cytoplasm of lymphocytes (7), inducing lymphoblastoid transformation resulting in clonal expansion of the infected cell (8,9). These transformed cells, primarily T cells, disseminate to lymphoid and nonlymphoid tissues, including the lung, kidney, and, intestine, where they mimic the behavior of lymphoid tumors (10,11). Remarkably unlike true lymphomas, T. parva-induced transformation can be reversed by killing the parasite (9,(10)(11)(12).…”

Section: Introductionmentioning

confidence: 99%

“…These transformed cells, primarily T cells, disseminate to lymphoid and nonlymphoid tissues, including the lung, kidney, and, intestine, where they mimic the behavior of lymphoid tumors (10,11). Remarkably unlike true lymphomas, T. parva-induced transformation can be reversed by killing the parasite (9,(10)(11)(12). This drug-induced reversal to normal lymphocyte regulation indicates that T. parva alone is sufficient and responsible for transformation.…”

Section: Introductionmentioning

confidence: 99%

Parasite-mediated nuclear factor κB regulation in lymphoproliferation caused byTheileria parva infection

Palmer

Machado²,

Fernández³

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

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one of the authors regrets that she inadvertently omitted references to the computer program and protein potential function that the authors used for their simulations of barnase cited above. The following sentence should have been the first sentence of the Methods section: Molecular dynamics simulations were performed with the program ENCAD (44) and the potential energy function of Levitt et al. (45).

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“…Perhaps of more relevance to the cause of death is the infiltration of other tissues, particularly the lungs and gastro-intestinal tract, with parasitised lymphoblasts, and severe pulmonary oedema and associated dyspnoea are commonly observed late in infection (47). A striking feature of the histological appearance of lymphoid tissues at the time of death is a marked depletion of lymphocytes (48,51), presumably the result of the extensive lymphocytolysis which can be observed in the later stages of the disease and which is not restricted to parasitised cells (7,47). It is likely that the invasion of haemopoietic tissues by parasitised cells during the course of the disease also contributes to the depletion of cells in lymphoid organs.…”

Section: Pathogenesismentioning

confidence: 99%

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

McKeever¹,

Morrison²

1990

Rev. Sci. Tech. OIE

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Summary: 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 parasitespecific 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.KEYWORDS: Antibody -Antigen -Antigen delivery -Antigen processingCell-mediated immunity -Cross-protection -Immunisation -Immunity -MHCrestriction -Parasite -Pathology -Theileria -Vaccine. THE PARASITE AND ITS LIFE CYCLETheileria parva is a haemoprotozoan parasite which infects cattle and buffalo in large areas of Eastern, Central and Southern Africa. The sporozoite stage of the parasite is transmitted by the three-host tick Rhipicephalus appendiculatus and invades lymphocytes, where its development to the schizont stage is associated with uncontrolled proliferation of the cell. The capacity of the parasite to associate with the mitotic spindle (78) ensures that schizonts are passed on to successive generations of daughter cells, giving rise to a clonal expansion of the initially parasitised population. A proportion of parasitised cells undergo merogony, resulting in disruption of the lymphocyte and release of merozoites into the blood. Merozoites then invade erythrocytes and differentiate into piroplasms which constitute the infective stage for the tick. PATHOGENESISInfection of cattle with T. parva gives rise to an acute lymphoproliferative disorder known as East Coast fever (ECF), and the course of this disease has been well characterised in experimentally-infected animals (47). At approximately 8 days after infection, schizont-infected cells are detectable in the lymph node which drains the site of inoculation. Parasitised cells can be detected in other lymphoid tissues throughout th...

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Theileria parva: Kinetics of infection in the lymphoid system of cattle

Cited by 52 publications

References 8 publications

Theileria parva-Transformed T Cells Show Enhanced Resistance to Fas/Fas Ligand-Induced Apoptosis

Theileria parva-Transformed T Cells Show Enhanced Resistance to Fas/Fas Ligand-Induced Apoptosis

Parasite-mediated nuclear factor κB regulation in lymphoproliferation caused byTheileria parva infection

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

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