Resident Memory T cells in Leishmaniasis
Resident Memory T cells in Leishmaniasis
批准号:
9916704
负责人:
PHILLIP SCOTT
金额:
$40.25万
依托单位国家:
美国
项目类别:
财政年份:
2016
资助国家:
美国
项目状态:
已结题
起止时间:
2016-05-16 至 2022-04-30
关键词:
AdjuvantAdoptive TransferAntigensCD4 Positive T LymphocytesCell Differentiation processCellsCellular ImmunityCutaneousDevelopmentDiseaseEragrostisFutureGenerationsGenus MycobacteriumGoalsHumanImmunityImmunizationInfectionInflammatoryInterferon Type IIInterferonsLeishmaniaLeishmania majorLeishmaniasisLesionLinkMediatingMemoryMethodsMusNatureParasite ControlParasitesPlasmodiumPrimary InfectionProteinsResistanceResolutionRoleRouteSeedsSkinSkin graftSourceT cell differentiationT cell responseT memory cellT-LymphocyteT-Lymphocyte SubsetsTestingToxoplasmaTranslatingVaccinationVaccinesVacciniaVaccinia viruscell motilitydesigneffector T cellmigrationmonocyteneglected tropical diseasespathogenpathogenic microberecruitresponsesuccesstoolvaccine developmentvaccine efficacyvaccine evaluationvaccine-induced immunity
中文摘要
细胞内微生物病原体(如分枝杆菌)有效疫苗的开发,
英文摘要
The development of effective vaccines for intracellular microbial pathogens, such as mycobacteria,
toxoplasma, plasmodium, and leishmania, remains an elusive goal. Despite substantial efforts to define the
mechanisms required for resistance, develop new adjuvants, and identify protective antigens, the long-lived
cellular immunity that can be generated in response to infection is not always recapitulated by vaccination.
For example, in spite of the strong immunity that develops following an infection with leishmania, efforts to
develop a vaccine for human leishmaniasis have been unsuccessful. Lack of success is due in part to the
limited understanding of the T cells that mediate protection. While we have identified circulating T cell
subsets that contribute to immunity in leishmaniasis (1), these circulating T cells fail to provide the level of
immunity observed in mice that have resolved a primary infection with L. major. Using a combination of skin
grafting and adoptive transfers, however, we found that leishmania-responsive IFN-γ producing CD4+ T
cells resident in the skin are the missing link required for optimal protective immunity (2). We propose to
identify how they are generated and maintained in the skin, determine how they promote immunity, and
target them in a leishmanial vaccine. These studies are important for leishmaniasis, and have broad
implications for vaccine development against other pathogens. In Aim 1 we will define the factors that
regulate the accumulation of CD4+ resident memory T cells in the skin following resolution of a primary
infection. These studies have direct relevance to vaccine development, as they will define what will be
required for generating resident memory T cells. In Aim 2, we focus on the mechanisms by which resident
memory T cells mediate protection. Here we will identify the effector T cells that synergize with resident
memory T cells to mediate protection, and determine if resident memory T cells help to amplify the
generation of T effector cells. Finally, in Aim 3 we will translate this information into an experimental
vaccine. We will create a recombinant vaccinia virus expressing a leishmanial antigen, and assess the
protection induced by this vaccine and qualitatively and quantitatively define the T cells that contribute to
that protection.
期刊论文(2)
专著(0)
科研奖励(0)
会议论文
DOI:
10.1371/journal.ppat.1006349
发表时间:
2017-04
期刊:
PLoS pathogens
影响因子:
6.7
作者:
[Glennie ND, Volk SW, Scott P]
通讯作者:
Scott P
Long-Lived Skin-Resident Memory T Cells Contribute to Concomitant Immunity in Cutaneous Leishmaniasis.
长寿命皮肤记忆 T 细胞有助于皮肤利什曼病的伴随免疫。
DOI:
10.1101/cshperspect.a038059
发表时间:
2020
期刊:
Cold Spring Harbor perspectives in biology
影响因子:
7.2
作者:
[Scott,Phillip]
通讯作者:
Scott,Phillip
2023 Woods Hole Immunoparasitology Meeting
-
批准号:10680864
-
项目类别:
-
资助金额:$0.7万
-
财政年份:2023
-
负责人:PHILLIP SCOTT
-
依托单位:
2022 WOODS HOLE IMMUNOPARASITOLOGY MEETING
-
批准号:10458244
-
项目类别:
-
资助金额:$0.6万
-
财政年份:2022
-
负责人:PHILLIP SCOTT
-
依托单位:
CD8 T cell-dependent pathways leading to immunopathology in cutaneous leishmaniasis
-
批准号:10329958
-
项目类别:
-
资助金额:$55.78万
-
财政年份:2020
-
负责人:PHILLIP SCOTT
-
依托单位:
CD8 T cell-dependent pathways leading to immunopathology in cutaneous leishmaniasis
-
批准号:10556387
-
项目类别:
-
资助金额:$55.78万
-
财政年份:2020
-
负责人:PHILLIP SCOTT
-
依托单位:
23rd Annual Woods Hole Immunoparasitology (WHIP) Meeting
-
批准号:9750405
-
项目类别:
-
资助金额:$0.75万
-
财政年份:2019
-
负责人:PHILLIP SCOTT
-
依托单位:
20th Annual Woods Hole Immunoparasitology Meeting
-
批准号:9126050
-
项目类别:
-
资助金额:$0.5万
-
财政年份:2016
-
负责人:PHILLIP SCOTT
-
依托单位:
Annual Woods Hole Immunoparasitology (WHIP) Meeting
-
批准号:8899229
-
项目类别:
-
资助金额:$0.5万
-
财政年份:2015
-
负责人:PHILLIP SCOTT
-
依托单位:
Protective and Pathologic Roles for CD8+ T cells in Leishmaniasis
-
批准号:8758136
-
项目类别:
-
资助金额:$40.0万
-
财政年份:2014
-
负责人:PHILLIP SCOTT
-
依托单位:
Protective and Pathologic Roles for CD8+ T cells in Leishmaniasis
-
批准号:9300849
-
项目类别:
-
资助金额:$40.0万
-
财政年份:2014
-
负责人:PHILLIP SCOTT
-
依托单位:
Protective and Pathologic Roles for CD8+ T cells in Leishmaniasis
-
批准号:8895257
-
项目类别:
-
资助金额:$40.0万
-
财政年份:2014
-
负责人:PHILLIP SCOTT
-
依托单位:
Annual Woods Hole Immunoparasitology (WHIP) Meeting
-
批准号:8716279
-
项目类别:
-
资助金额:$1.0万
-
财政年份:2014
-
负责人:PHILLIP SCOTT
-
依托单位:
Resident memory T cells in leishmaniasis
-
批准号:8826680
-
项目类别:
-
资助金额:$20.0万
-
财政年份:2014
-
负责人:PHILLIP SCOTT
-
依托单位:
Annual Woods Hole Immunoparasitology (WHIP) Meeting
-
批准号:8257234
-
项目类别:
-
资助金额:$0.8万
-
财政年份:2012
-
负责人:PHILLIP SCOTT
-
依托单位:
Annual Woods Hole Immunoparasitology (WHIP) Meeting
-
批准号:8062912
-
项目类别:
-
资助金额:$1.0万
-
财政年份:2011
-
负责人:PHILLIP SCOTT
-
依托单位:
Myeloid-lineage cells and immunopathology in Leishmania braziliensis
-
批准号:8391271
-
项目类别:
-
资助金额:$57.69万
-
财政年份:2010
-
负责人:PHILLIP SCOTT
-
依托单位:
The Role of Innate Cells in the Pathogenesis of Leishmania Braziliensis Infection
-
批准号:8816766
-
项目类别:
-
资助金额:$35.0万
-
财政年份:2010
-
负责人:PHILLIP SCOTT
-
依托单位:
The Role of Innate Cells in the Pathogenesis of Leishmania Braziliensis Infection
-
批准号:9198979
-
项目类别:
-
资助金额:$34.66万
-
财政年份:2010
-
负责人:PHILLIP SCOTT
-
依托单位:
Myeloid-lineage cells and immunopathology in Leishmania braziliensis
-
批准号:7900707
-
项目类别:
-
资助金额:$63.69万
-
财政年份:2010
-
负责人:PHILLIP SCOTT
-
依托单位:
Myeloid-lineage cells and immunopathology in Leishmania braziliensis
-
批准号:8197000
-
项目类别:
-
资助金额:$60.16万
-
财政年份:2010
-
负责人:PHILLIP SCOTT
-
依托单位:
Myeloid-lineage cells and immunopathology in Leishmania braziliensis
-
批准号:8586461
-
项目类别:
-
资助金额:$57.21万
-
财政年份:2010
-
负责人:PHILLIP SCOTT
-
依托单位:
海外基金