Human Gene Set: GSE32128_INOS_DEPENDENT_VS_INOS_INDEPENDENT_ACTIVATED_TCELL_DN


Standard name GSE32128_INOS_DEPENDENT_VS_INOS_INDEPENDENT_ACTIVATED_TCELL_DN
Systematic name M8602
Brief description Genes down-regulated in T cell activation mechanism that was NOS2 [GeneID=4843] dependent versus NOS2 [GeneID=4843] independent activation.
Full description or abstract Comparison of two Chlamydia-specific CD4 T cells that are dependent on iNOS to terminate Chlamydia replication in epithelial cells to two Chlamydia-specific CD4 T cells that are iNOS-independent: Chlamydia trachomatis urogenital serovars replicate predominately in epithelial cells lining the reproductive tract. This tissue tropism poses a unique challenge for the host immune system and vaccine development. Studies utilizing the Chlamydia muridarum mouse model have shown that CD4 T cells are critical and sufficient to clear primary genital tract infections. In vitro studies have shown that CD4 T cells terminate the infection in epithelial cells by up regulating epithelial iNOS transcription and nitric oxide production via IFN-gamma and T cell-epithelial cell interactions mediated by LFA-1-ICAM-1. This mechanism however is not critical as iNOS-deficient mice clear infections normally, and IFN-gamma deficient mice clear 99.9% of the infection with near normal kinetics. We recently showed that a subset of Chlamydia-specific CD4 T cell clones were able to terminate replication in epithelial cells using a mechanism that was independent of iNOS and IFN-gamma. That mechanism did not require physical lysis of infected cells, but instead required T cell degranulation. In this study we advanced that work using gene expression microarrays to compare CD4 T cell clones that are able to terminate epithelial replication via an iNOS-independent mechanism to iNOS-dependent CD4 T cell clones. Micro array experiments showed that Plac8 was differentially expressed by the T cell clones having the iNOS-independent mechanism. Plac8-deficient mice had significantly delayed clearance of C. muridarum genital tract infections, and that the large majority of Plac8-deficient mice treated with the iNOS-inhibitor N-monomethyl-L-arginine (MLA) were unable to resolve a C. muridarum genital tract infection over 8 weeks. These results demonstrate that there are two independent and redundant T cell mechanisms for clearing C. muridarum genital tract infections; one mechanism dependent on iNOS, the other mechanism dependent on Plac8. While T cells subsets have been defined by cytokine profiles, there are important subdivisions by effector functions, in this case CD4Plac8.
Collection C7: Immunologic Signature
      IMMUNESIGDB: ImmuneSigDB
Source publication Pubmed 22238459   Authors: Johnson RM,Kerr MS,Slaven JE
Exact source GSE32128_2969_200_DN
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Source species Mus musculus
Contributed by Jernej Godec (Dana-Farber Cancer Institute)
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identifier namespace		 HUMAN_GENE_SYMBOL
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Version history 7.3: Moved to ImmuneSigDB sub-collection.


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