Unknown,Transcriptomics,Genomics,Proteomics

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Distinguishing innate memory CD8+ T from homeostatically expanded CD8+ T cells

ABSTRACT: Innate memory phenotype (IMP) CD8+ T cells are non-conventional αβ T cells exhibiting features of innate immune cells, and are significantly increased in the absence of non-receptor tyrosine kinase ITK. Their developmental path and function are not clear, particularly whether they can contribute to antigen specific responses. We found that WT bone marrow gives rise to IMP CD8+ T cells in irradiated MHCI-/- recipients, resembling those in Itk-/- mice determined by expression of surface markers. However, CD8+ T cells share similar expression of memory markers. We used microarrays to compare the global programme of gene expression to determine whether the CD8+ T cells selected by hematopoietic MHCI are IMP CD8+ T cells as observed in the absence of ITK, or the result of homeostatic expansion of T cell contamination in the donor bone marrow. Through analysis of global gene expression correlation and differential expression, we determined that hematopoietic MHCI dependent IMP CD8+ T cells generated in irradiated MHCI-/- recipients, resemble those in Itk-/- mice, but distinct from CD8+ T cells derived via homeostatic proliferation. Cell sorting was performed using a FACSAria Cell Sorter (BD Biosciences, San Diego, CA). IMP CD8+ T cells (TCRβ+CD8α+CD44hi) were sorted from splenocytes of WT→MHCI-/- chimeras 8 weeks post transplantation and 8-week old Itk-/- mice. To generate HP cells, naïve CD8+ T cells (TCRβ+CD8α+CD44lo) were sorted and injected into Rag1-/- recipients (0.5 million /mouse, retro-orbital injection), followed by sorting of TCRβ+CD8α+ splenocytes 8 weeks post adoptive transfer. We sought to compare cells with the same gender and age, thus all donors were female, and ages (absolute age for Itk null and age post transfer for chimeras and HP model) were 8 weeks.

ORGANISM(S): Mus musculus

SUBMITTER: Weishan Huang

PROVIDER: E-GEOD-41482 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Cutting edge: innate memory CD8+ T cells are distinct from homeostatic expanded CD8+ T cells and rapidly respond to primary antigenic stimuli.

Huang Weishan W Hu Jianfang J August Avery A

Journal of immunology (Baltimore, Md. : 1950) 20130213 6

Innate memory phenotype (IMP) CD8(+) T cells are nonconventional αβ T cells exhibiting features of innate immune cells and are significantly increased in the absence of ITK. Their developmental path and function are not clear. In this study, we show hematopoietic MHC class I (MHCI)-dependent generation of Ag-specific IMP CD8(+) T cells using bone marrow chimeras. Wild-type bone marrow gives rise to IMP CD8(+) T cells in MHCI(-/-) recipients, resembling those in Itk(-/-) mice, but distinct from t ...[more]

PMID: 23408840

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Project description:Innate memory phenotype (IMP) CD4+ T cells are non-conventional Î±Î² T cells exhibiting features of innate immune cells, characterized as CD44high and CD62Llow in periphery. It is recently reported by our group that bone marrow chimeric mice lacking thymic MHCI expression develop predominantly IMP CD8+ T cells, while those lacking hematopoietic MHCI develop predominantly naÃ¯ve CD8+ T cells. Here we perform hirarchical clustering analysis and found that CD4+ T cells share similar property: chimeras lacking thymic MHCII gave rise to predominantly CD4+ T cells that resemble IMP CD4+ T cells observed in WT mice, and vice versa, chimeras lacking hematopoietic MHCII had a majority of naÃ¯ve-like CD4+ T cells resembling naÃ¯veCD4+ T cells seen in WT mice. We used microarrays to compare the global programme of gene expression to determine whether the hematopoietic MHCII selected CD4+ T cells are IMP, and whether the thymic MHCII selected CD4+ T cells are naÃ¯ve CD4+ T cells as observed in WT mice. Through hierarchical clustering and analysis of global gene differential expression, we determined that hematopoietic MHCII dependent IMP CD4+ T cells generated from WT bone marrow transplanted into irradiated MHCII-/- recipients, resemble IMP CD4+ T cells in WT mice, while naÃ¯ve CD4+ T cells generated from MHCII-/- bone marrow transplanted into irradiated WT recipients, resemble naÃ¯ve CD4+ T cells in WT mice. Cell Sorting was performed using a Cytopeia Influx Cell Sorter. Chimeric IMP (CD45.1+TCRÎ²+CD4+CD44highCD62Llow) CD4+ T cells were sorted from splenocytes of CD45.1+WTâCD45.2+MHCII-/- chimeras (WM IMP CD4), and chimeric naÃ¯ve (CD45.2+TCRÎ²+CD4+CD44lowCD62Lhigh) CD4+ T cells were sorted from splenocytes of CD45.2+MHCII-/- â CD45.1+WT chimeras (MW naÃ¯ve CD4) respectively, 8 weeks post transplantation. WT IMP (TCRÎ²+CD4+CD44highCD62Llow) and naÃ¯ve (TCRÎ²+CD4+CD44lowCD62Lhigh) CD4+ T cells were sorted from splenocytes of 8-week old WT mice.

Dataset Information

Distinguishing innate memory CD8+ T from homeostatically expanded CD8+ T cells

Publications

Cutting edge: innate memory CD8+ T cells are distinct from homeostatic expanded CD8+ T cells and rapidly respond to primary antigenic stimuli.

Similar Datasets

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