Cytokines inhibit the development of trophozoite‐infected cells of <i>Theileria annulata</i> and <i>Theileria parva</i> but enhance the proliferation of macroschizont‐infected cell lines

Preston, Patricia M.; Brown, C.G.D.; Richardson, Wendy

doi:10.1111/j.1365-3024.1992.tb00456.x

Cited by 37 publications

(19 citation statements)

References 17 publications

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“…The high number of cytokine responders that succumbed to the challenge infection indicates that ex vivo IFN-␥ responses do not serve as a predictive marker of protection against severe disease or fatality. This observation is notable in the context of previous studies, which demonstrated an inhibitory effect of IFN-␥ on the development of the early schizont stage in vitro (20). Our data suggest that vaccineinduced CD8 ϩ lytic responses may contribute to survival from a lethal challenge infection and highlight possible distinct roles of IFN-␥-secreting and lytic CD8 ϩ T cells in immunity against ECF.…”

Section: Ctl Target Antigens Recognized By T Cells From Immune Cattlesupporting

confidence: 78%

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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Section: Ctl Target Antigens Recognized By T Cells From Immune Cattlesupporting

confidence: 78%

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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“…A possible role for CD4 + -positive T-cells in immunity to T. annulata may involve their production of macrophage-activating cytokines. Indeed, cytostatic macrophages have been demonstrated in T. annulataimmune cattle (Preston 1981;Preston and Brown 1985;Preston et al 1992b). On the basis of the capacity of such macrophages to produce TNF-a (Preston et al 1993) and NO (Visser et al 1995), it has been suggested that CD4 + cells produce IFN-c, which participates in the activation of such macrophages to produce NO and to kill the schizonts (Preston et al 1997;Richardson et al 1998).…”

Section: T-helper Cellsmentioning

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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“…More importantly, activated CD 4 T cells produce cytokines such as IL-2 and IFN-γ required for the clonal expansion of CTLs (Ahmed and Mehlhorn 1999;Forsyth et al 1997). In addition, IFN-γ stimulates bovine macrophages to synthesize TNF-α (Preston et al 1993), which is regarded as a modulator cytokine in host defense against protozoal Infections (Aggarwal et al 1985), leading to inhibition of trophozoite-infected cells as well as cytotoxic effects on macroschizontinfected cells (Preston et al 1992.…”

Section: Introductionmentioning

confidence: 99%

The correlations among serum tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ) and sialic acids with peripheral lymphocytes in bovine tropical theileriosis

et al. 2010

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The infection with protozoan parasite Theileria annulata induces changes triggering the activation and/or proliferation of the host lymphocytes. In order to find out the possible correlations among peripheral circulatory lymphocytes, cytokine activities and the level of sialic acids, 50 dairy Holstein cattle, naturally infected with T. annulata, were divided into 4 subgroups according to their parasitemia rates (<1%, 1-3%, 3-5% and >5%). Also, ten non-infected cattle were sampled as control group. Blood samples were taken from jugular vein into acid citrate dextrose-containing tubes for measuring hematological parameters and B and T (CD(4) and CD(8)) cell populations and without anticoagulant for TNF-alpha, IFN-gamma and sialic acid concentrations. Remarkable decreases observed in red blood cells (RBCs), white blood cells (WBCs) and packed cell volume (PCV) in infected cattle compared to healthy ones (P < 0.05). Also, with increase in parasitemia rate, total lymphocytes and monocytes alleviated in the diseased groups. By contrast, total neutrohpils and the concentrations of TNF-alpha, IFN-gamma and total sialic acids were significantly elevated (P < 0.05) in infected animals. Accordingly, the circulatory populations of CD(4) and CD(8) T cells and B cells showed a substantial decrease, while a significant increase was observed in T (CD(4) and CD(8)) cells in cattle infected with <1% parasitemia rates. Decreased circulatory T cell population shows the ineffective responses of T cells to the stimulatory cytokines such as IFN-gamma or TNF-alpha. On the other hand, the elevation of cytokines (particularly IFN-gamma) and sialic acids have presumably an inhibitory role on circulatory B cell population in infected cattle. In addition, a high level of sialic acid concentration indicates the probable role of sialic acid to regulate the parasite-host cell adhesion during sporozoites invasion.

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Cytokines inhibit the development of trophozoite‐infected cells of Theileria annulata and Theileria parva but enhance the proliferation of macroschizont‐infected cell lines

Cited by 37 publications

References 17 publications

Theileria parvacandidate vaccine antigens recognized by immune bovine cytotoxic T lymphocytes

Theileria parvacandidate vaccine antigens recognized by immune bovine cytotoxic T lymphocytes

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

The correlations among serum tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ) and sialic acids with peripheral lymphocytes in bovine tropical theileriosis

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