Cytotoxic T‐cells elicited in cattle challenged with<i>Theileria parva</i>(Muguga): evidence for restriction by class I MHC determinants and parasite strain specificity

Morrison, W. Ivan; Goddeeris, Bruno; Teale, A.J.; Groocock, C M; Kemp, Stephen J.; Stagg, D.A.

doi:10.1111/j.1365-3024.1987.tb00530.x

Cited by 87 publications

(57 citation statements)

References 37 publications

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“…Manufacture and delivery of the live ECF vaccine is difficult to sustain, but it has enabled elucidation of the dominant protective immune response against the disease. Kinetic and adoptive cell transfer studies (5,6) have demonstrated that protection of cattle is mediated by MHC class I-restricted CD8 ϩ cytotoxic T lymphocytes (CTL) that destroy schizontinfected lymphocytes, the pathogenic life-cycle stage of T. parva. In addition, there is a strong correlation between the specificity of the CTL response and cross-immunity profiles of distinct parasite strains (2).…”

mentioning

confidence: 99%

Theileria parvacandidate vaccine antigens recognized by immune bovine cytotoxic T lymphocytes

Graham

Pellé

Honda

et al. 2006

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

115

131

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East Coast fever, caused by the tick-borne intracellular apicomplexan parasite Theileria parva, is a highly fatal lymphoproliferative disease of cattle. The pathogenic schizont-induced lymphocyte transformation is a unique cancer-like condition that is reversible with parasite removal. Schizont-infected cell-directed CD8 ؉ cytotoxic T lymphocytes (CTL) constitute the dominant protective bovine immune response after a single exposure to infection. However, the schizont antigens targeted by T. parva-specific CTL are undefined. Here we show the identification of five candidate vaccine antigens that are the targets of MHC class I-restricted CD8 ؉ CTL from immune cattle. CD8 ؉ T cell responses to these antigens were boosted in T. parva-immune cattle resolving a challenge infection and, when used to immunize naïve cattle, induced CTL responses that significantly correlated with survival from a lethal parasite challenge. These data provide a basis for developing a CTL-targeted anti-East Coast fever subunit vaccine. In addition, orthologs of these antigens may be vaccine targets for other apicomplexan parasites.cattle ͉ East Coast fever ͉ immunoscreening ͉ protozoan parasite ͉ vaccination A single inoculation with a potentially lethal dose of Theileria parva sporozoites and simultaneous treatment with a longacting oxytetracycline induces solid immunity to homologous and, in certain instances, heterologous parasite challenge (1, 2). This methodology has been adopted as a live vaccine for the control of East Coast fever (ECF) (3). The long-lasting immunity to ECF contrasts with the partial immunity to malaria that develops after only several years of exposure to T. parva-related Plasmodium spp. (4). Manufacture and delivery of the live ECF vaccine is difficult to sustain, but it has enabled elucidation of the dominant protective immune response against the disease. Kinetic and adoptive cell transfer studies (5, 6) have demonstrated that protection of cattle is mediated by MHC class I-restricted CD8 ϩ cytotoxic T lymphocytes (CTL) that destroy schizontinfected lymphocytes, the pathogenic life-cycle stage of T. parva. In addition, there is a strong correlation between the specificity of the CTL response and cross-immunity profiles of distinct parasite strains (2). The identification of schizont antigens targeted by CTL from T. parva-immune cattle has been elusive but should pave the way for the development of a subunit vaccine against ECF and provide a long-term solution to a socioeconomically important constraint to livestock agriculture in Africa (7). We adopted two approaches to antigen identification, both dependent on screening of transiently transfected antigenpresenting cells with fully characterized CTL (8, 9) from live vaccine-immunized cattle of diverse bovine leukocyte antigen (BoLA) MHC class I genotypes. First, in a targeted gene approach, we immunoscreened genes that were predicted by using preliminary sequence data from one of the four T. parva chromosomes (10) to contain a secretion signal. The approach was ...

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confidence: 99%

Theileria parvacandidate vaccine antigens recognized by immune bovine cytotoxic T lymphocytes

Graham

Pellé

Honda

et al. 2006

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

115

131

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“…Another feature of these results was that in most of the animals the restriction of the response was biased towards one or other of the haplotypes. Indeed, of the BoLA specificities represented in the trial, some were consistently seen to dominate over the others as restricting elements (55). This effect was interpreted as being a reflection of a hierarchy in dominance among the BoLA products which restrict the response.…”

Section: Cellular Immunitymentioning

confidence: 91%

“…In a study which involved the assessment of cytolytic activity in the PBM of ten immune heterozygous animals after challenge with homologous sporozoites, it became clear that activity in individual animals was restricted to infected targets derived from animals which shared MHC class I specificities (55). The observation that a MAB specific for a monomorphic determinant on bovine class I molecules was capable of significantly inhibiting this activity, while two class II-specific MAB had no effect, confirmed that class I MHC products were indeed the restricting elements.…”

Section: Cellular Immunitymentioning

confidence: 99%

“…The specificity of the response in five animals immunised with T. parva (Muguga) and one animal immunised with T. parva (Marikebuni) was examined in detail using autologous targets infected with either parasite (52,53,55). Cytotoxic T cells prepared from the animal immunised with the Marikebuni stock were capable of killing targets infected with either parasite.…”

Section: Parasite Strain Specificitymentioning

confidence: 99%

“…These studies have made use of the differences in the specificity of immune responses engendered by challenge with the Muguga and Marikebuni stocks of T. parva. Cattle immunised with T. parva (Marikebuni) are immune to challenge with both stocks, whereas a proportion of cattle immunised with T. parva (Muguga) are susceptible to challenge with the Marikebuni stock (46).The specificity of the response in five animals immunised with T. parva (Muguga) and one animal immunised with T. parva (Marikebuni) was examined in detail using autologous targets infected with either parasite (52,53,55). Cytotoxic T cells prepared from the animal immunised with the Marikebuni stock were capable of killing targets infected with either parasite.…”

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confidence: 99%

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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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Lymphocytes infected with Theileria parva require both cell‐cell contact and growth factor to proliferate

Dobbelaere¹,

Roditi²,

Coquerelle³

et al. 1991

Eur J Immunol

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Lymphocytes infected with the intracellular parasite Theileria parva proliferate continuously as lymphoblastoid cell lines. We have previously shown that the continuous proliferation of the T. parva-infected (Tpi) cell line TpM(803) is mediated in part by an autocrine mechanism (Dobbelaere, D. A. E. et al., Proc. Natl. Acad. Sci. USA 1988. 85:4730). We now report that continuous proliferation also requires surface stimulation through cell-cell contact. Under standard culture conditions this surface stimulus is provided by the infected cells themselves, but it can also be provided by uninfected lymphocytes or macrophages. The ability to respond to surface stimulation is critically dependent on the presence of the parasite in the host cell and is lost within 48 h after the elimination of the parasite from the host cell cytoplasm by treatment with the theilericidal drug BW720c. Tpi cells also secrete a growth factor which is able to support the proliferation of diluted Tpi cells. Growth factor secretion is rapidly lost upon elimination of the parasite. Moreover, inhibition experiments using anti-interleukin 2 (IL 2) antibodies show that IL 2 is involved in the proliferation of the Tpi cell lines TpM(803) and IN10. T cell proliferation is dependent on a number of costimulatory signals which are normally provided by accessory cells. The finding that Tpi cells can mutually stimulate each other to grow in the absence of conventional accessory cells helps to explain how they can escape the normal constraints on T cell growth, allowing them to invade and multiply in non-lymphoid as well as lymphoid tissues.

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

Cited by 87 publications

References 37 publications

Theileria parvacandidate vaccine antigens recognized by immune bovine cytotoxic T lymphocytes

Theileria parvacandidate vaccine antigens recognized by immune bovine cytotoxic T lymphocytes

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

Lymphocytes infected with Theileria parva require both cell‐cell contact and growth factor to proliferate

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