Generating mouse model with predominant naïve or innate memory phenotype CD4+ T cells
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ABSTRACT: Innate memory phenotype (IMP) CD4+ T cells are non-conventional αβ 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 naïve 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 naïve-like CD4+ T cells resembling naïveCD4+ 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 naïve 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 naïve CD4+ T cells generated from MHCII-/- bone marrow transplanted into irradiated WT recipients, resemble naïve CD4+ T cells in WT mice. Cell Sorting was performed using a Cytopeia Influx Cell Sorter. Chimeric IMP (CD45.1+TCRβ+CD4+CD44highCD62Llow) CD4+ T cells were sorted from splenocytes of CD45.1+WTâCD45.2+MHCII-/- chimeras (WM IMP CD4), and chimeric naïve (CD45.2+TCRβ+CD4+CD44lowCD62Lhigh) CD4+ T cells were sorted from splenocytes of CD45.2+MHCII-/- â CD45.1+WT chimeras (MW naïve CD4) respectively, 8 weeks post transplantation. WT IMP (TCRβ+CD4+CD44highCD62Llow) and naïve (TCRβ+CD4+CD44lowCD62Lhigh) CD4+ T cells were sorted from splenocytes of 8-week old WT mice.
ORGANISM(S): Mus musculus
SUBMITTER: Weishan Huang
PROVIDER: E-GEOD-46892 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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