Influence of CD4+CD25+ T cells on Plasmodium berghei NK65 infection in BALB/c mice

Long, Ton That Ai; Nakazawa, Shozo; Onizuka, Shozaburo; Huaman, Maria Cecilia; Kanbara, Hiroji

doi:10.1016/s0020-7519(02)00261-8

Cited by 80 publications

(70 citation statements)

References 36 publications

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“…At an early time after Ab treatment (day 28), pre-erythrocytic protection was also observed in the Ab-treated, nonvaccinated animals. We observed identical parasite growth curves in anti-CD25-treated or untreated naive mice that were challenged with blood-stage P. berghei parasites, in agreement with a previous study (47), demonstrating that anti-CD25-mediated protection occurs at the liver stage of P. berghei infection. However, when challenge is performed at 42 or 52 days after Ab treatment, at a time when the anti-CD25 Ab is undetectable in the serum (19) and immune responses in immunized, Abtreated animals are still at a high level (Fig.…”

Section: Discussionsupporting

confidence: 91%

Anti-CD25 Antibody Enhancement of Vaccine-Induced Immunogenicity: Increased Durable Cellular Immunity with Reduced Immunodominance

Moore

Gallimore

Draper

et al. 2005

The Journal of Immunology

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An efficacious vaccine strategy must be capable of inducing strong responses of an appropriate phenotype that are long lasting and sufficiently broad to prevent pathogen escape mechanisms. In the present study, we use anti-CD25 mAb to augment vaccine-induced immunity in mice. We demonstrate that coformulation of Ab and poxviral- or adenoviral-vectored vaccines induces significantly increased T cell responses to a malaria Ag; prior anti-CD25 Ab administration was not required for this effect. Furthermore, this vaccination approach subverts immunodominant epitope hierarchies by enhancing responses to subdominant epitopes induced by recombinant modified vaccinia virus Ankara immunization. Administration of anti-CD25 with a vaccine also induces more durable immunity compared with vaccine alone; significantly higher T cell responses were observed 100 days after the primary immunization. Enhanced immunogenicity is observed for multiple vaccine types with enhanced CD4+ and CD8+ T cell responses induced by bacillus Calmette-Guérin and a recombinant subunit protein vaccine to hepatitis B virus and with multiple Ags of tumor, viral, bacterial, and parasitic origin. Vaccine strategies incorporating anti-CD25 lead to improved protection against pre-erythrocytic malaria challenge. These data underpin new strategies for the design and development of more efficacious vaccines in clinical settings.

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Section: Discussionsupporting

confidence: 91%

Anti-CD25 Antibody Enhancement of Vaccine-Induced Immunogenicity: Increased Durable Cellular Immunity with Reduced Immunodominance

Moore

Gallimore

Draper

et al. 2005

The Journal of Immunology

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“…Depending on the mouse-parasite combination studied, Treg were found to contribute to disease severity [24,25], or to prevent severe symptoms [26,28] or, to have no effect on disease outcome at all [22,23,27]. In some cases, discordant results were observed even in very similar models [22,24,25,27].…”

Section: Cd25mentioning

confidence: 99%

“…Furthermore, a recent microarray study in Burkina Faso suggested that the reduced susceptibility to malaria observed in Fulani compared with sympatric ethnic groups may be linked to fewer or less functional Treg [21]. Taken together, these studies suggest that pre-existing levels of Treg may influence disease susceptibility.In several murine models of malaria, Treg are up-regulated upon infection [22][23][24][25][26][27], but whether or not (or in which direction) Treg may influence disease outcome is highly controversial. Depending on the mouse-parasite combination studied, Treg were found to contribute to disease severity [24,25], or to prevent severe symptoms [26,28] or, to have no effect on disease outcome at all [22,23,27].…”

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confidence: 99%

Homeostatic regulation of T effector to Treg ratios in an area of seasonal malaria transmission

et al. 2009

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An important aspect of clinical immunity to malaria is the ability to down-regulate inflammatory responses, once parasitaemia is under control, in order to avoid immunemediated pathology. The role of classical (CD4 CD127lo/À FOXP3 1 ) Treg in this process, however, remains controversial. Thus, we have characterized the frequency, phenotype and function of Treg populations, over time, in healthy individuals in The Gambia. We observed that both the percentage and the absolute number of CD4lo/À T cells were higher among individuals living in a rural village with highly seasonal malaria transmission than among individuals living in an urban area where malaria rarely occurs. These CD4 1 FOXP31 CD127 lo/À T cells exhibited an effector memory and apoptosis-prone phenotype and suppressed cytokine production in response to malaria antigen. Cells from individuals exposed to malaria expressed significantly higher levels of mRNA for forkhead box P3 and T-box 21 (T-BET) at the end of the malaria transmission season than at the end of the non-transmission season. Importantly, the ratio of T-BET to forkhead box P3 was remarkably consistent between populations and over time, indicating that in healthy individuals, a transient increase in Th1 responses during the malaria transmission season is balanced by a commensurate Treg response, ensuring that immune homeostasis is maintained.Key words: Human . Malaria . Regulation . T cells Supporting Information available online IntroductionA strong pro-inflammatory response, characterized by IFN-g and TNF-a, contributes to the initial killing and clearance of malariainfected RBC [1]. However, immune-mediated pathologypredominantly observed in non-immune and semi-immune subjects -has been linked to sustained and/or excessive inflammatory responses in animal malaria models [2] and human disease [3]. Indeed, ratios of inflammatory to regulatory cytokines seem to determine the severity of disease: low levels of and 8] have been associated with acute or severe malaria, and high ratios of IFN-g, TNF-a and IL-12 to TGF-b or IL-10 are associated with decreased risk of malaria infection but increased risk of clinical disease in those who do Ã These authors contributed equally to this work. 1288become infected [9,10]. Moreover, in vitro parasite-induced IFN-g production by PBMC is considerably lower among clinically immune individuals than among semi-immune subjects [11,12]. This has led to the hypothesis that the ability to down-regulate inflammatory responses -once parasitaemia is under control -is crucial to avoid immune-mediated pathology, and may therefore be an important feature of clinical immunity to malaria [3,13].The balance between pro-inflammatory and regulatory immune mechanisms is crucial in determining the outcome of many parasitic infections [13,14]: pro-inflammatory responses, though essential to clear infection, can also lead to severe disease and need to be very tightly regulated in order to maintain immune homeostasis.Treg, first characterised by a high level of CD25 expressi...

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“…For instance, Tregs suppress harmful immune pathogenesis caused by infection (6), and they contribute to the establishment of chronic infection instead of the elimination of pathogens, thus maintaining exposure of memory T cells to microbial Ags (7). With use of a murine model, we and others have demonstrated that the immune escape of malaria parasites requires activation of Tregs (8,9). Furthermore, Walther and colleagues found that up-regulation of Tregs correlates with rapid parasite growth during human malaria infection (10).…”

mentioning

confidence: 99%

Malaria Parasites Require TLR9 Signaling for Immune Evasion by Activating Regulatory T Cells

Hisaeda

Tetsutani

Imai

et al. 2008

The Journal of Immunology

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Malaria is still a life-threatening infectious disease that continues to produce 2 million deaths annually. Malaria parasites have acquired immune escape mechanisms and prevent the development of sterile immunity. Regulatory T cells (Tregs) have been reported to contribute to immune evasion during malaria in mice and humans, suggesting that activating Tregs is one of the mechanisms by which malaria parasites subvert host immune systems. However, little is known about how these parasites activate Tregs. We herein show that TLR9 signaling to dendritic cells (DCs) is crucial for activation of Tregs. Infection of mice with the rodent malaria parasite Plasmodium yoelii activates Tregs, leading to enhancement of their suppressive function. In vitro activation of Tregs requires the interaction of DCs with parasites in a TLR9-dependent manner. Furthermore, TLR9−/− mice are partially resistant to lethal infection, and this is associated with impaired activation of Tregs and subsequent development of effector T cells. Thus, malaria parasites require TLR9 to activate Tregs for immune escape.

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Influence of CD4+CD25+ T cells on Plasmodium berghei NK65 infection in BALB/c mice

Cited by 80 publications

References 36 publications

Anti-CD25 Antibody Enhancement of Vaccine-Induced Immunogenicity: Increased Durable Cellular Immunity with Reduced Immunodominance

Anti-CD25 Antibody Enhancement of Vaccine-Induced Immunogenicity: Increased Durable Cellular Immunity with Reduced Immunodominance

Homeostatic regulation of T effector to Treg ratios in an area of seasonal malaria transmission

Malaria Parasites Require TLR9 Signaling for Immune Evasion by Activating Regulatory T Cells

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