Dataset Information

WASp Is Essential for Effector-to-Memory conversion and for Maintenance of CD8+T Cell Memory.

ABSTRACT: Wiskott-Aldrich syndrome (WAS) is a rare X-linked primary immunodeficiency characterized by recurrent infections, micro thrombocytopenia, eczema, and a high incidence of autoimmunity and malignancy. A defect in the T cell compartment is thought to be a major cause of immunodeficiency in patients with WAS; However, whether the antigen specific T memory cell is altered has not been extensively studied. Here, we examined the expansion/contraction kinetics of CD8+ memory T cells and their maintenance in WASp-/- mice. The results showed that WAS protein (WASp) is not required for differentiation of CD8+ effector T cells; however, CD8+ T cells from WASp-/- mice were hyperactive, resulting in increased cytokine production. The number of CD8+ T memory cells decreased as mice aged, and CD8+ T cell recall responses and protective immunity were impaired. WASp-deficient CD8+ T cells in bone marrow chimeric mice underwent clonal expansion, but the resulting effector cells failed to survive and differentiate into CD8+ memory T cells. Taken together, these findings indicate that WASp plays an intrinsic role in differentiation of CD8+ memory T cells.

SUBMITTER: Liu Q

PROVIDER: S-EPMC6769127 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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WASp Is Essential for Effector-to-Memory conversion and for Maintenance of CD8<sup>+</sup>T Cell Memory.

Liu Qiao Q Zhang Liang L Shu Zhou Z Yu Tingting T Zhou Lina L Song Wenxia W Zhao Xiaodong X

Frontiers in immunology 20190924

Wiskott-Aldrich syndrome (WAS) is a rare X-linked primary immunodeficiency characterized by recurrent infections, micro thrombocytopenia, eczema, and a high incidence of autoimmunity and malignancy. A defect in the T cell compartment is thought to be a major cause of immunodeficiency in patients with WAS; However, whether the antigen specific T memory cell is altered has not been extensively studied. Here, we examined the expansion/contraction kinetics of CD8<sup>+</sup> memory T cells and their ...[more]

PMID: 31608063

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Project description:During a T cell response, naÃ¯ve CD8 T cells differentiate into effector cells. Subsequently, a subset of effector cells termed memory precursor effector cells (MPECs) further differentiates into functionally mature memory CD8 T cells. The transcriptional network underlying this carefully scripted process is not well understood. Here, we report that the transcription factor FoxO1 plays an integral role in facilitating effector to memory transition and functional maturation of memory CD4 and CD8 T cells. We find that FoxO1 is not required for differentiation of effector cells, but in the absence of FoxO1, memory CD8 T cells displayed features of scenescence and progressive attrition in polyfunctionality, which in turn led to impared recall responses and poor protective immunity. These data suggest that FoxO1 is essential for active maintenance of functional CD8 T cell memory and protective immunity. Under competing conditions in bone marrow Single-cell suspensions from splenocytes of eight samples WT (control) and FoxO1-/- (experimental) LCMV-immune mice were prepared using standard procedures. CD8 T cells were then isoloated using Thy1.2 (CD90.2) (30-H12) microbeads (Miltenyi Biotec). Cells were then stained with anti-CD8, anti-CD44 and Db/NP396 MHC class I tetramer. Activated (CD8+CD44hi), naive (CD8+CD44lo), and virus-specific CD8 T cells were sorted using FACSAria II instrument (BD Biosciences). The purity of the cells was >95%. Total RNA was extracted from the sorted cells by Trizol Reagent. RNA samples were reverse transcribed and Cy3-labeled cDNAs were hyrbidized to Agilent whole Mouse Genome Oligo Microarrays. Fluorscence signals were detected using Agilent's Microarray Scanner system, data was analyzed using the Rosetta Resolver gene expression data analysis system and genes with a fold change < and p-values <0.01 were identified. Microarray data discussed in the paper is focused on virus-specific memory CD8 T cells from samples WT_Tet_2 vs KO_Tet_2.

Dataset Information

WASp Is Essential for Effector-to-Memory conversion and for Maintenance of CD8+T Cell Memory.

Publications

WASp Is Essential for Effector-to-Memory conversion and for Maintenance of CD8<sup>+</sup>T Cell Memory.

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