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dc.contributor.authorPrince, Amanda L.
dc.contributor.authorWatkin, Levi B.
dc.contributor.authorYin, Catherine C
dc.contributor.authorSelin, Liisa K.
dc.contributor.authorKang, Joonso
dc.contributor.authorSchwartzberg, Pamela L.
dc.contributor.authorBerg, Leslie J.
dc.date2022-08-11T08:08:55.000
dc.date.accessioned2022-08-23T16:12:27Z
dc.date.available2022-08-23T16:12:27Z
dc.date.issued2014-07-15
dc.date.submitted2015-09-21
dc.identifier.citationJ Immunol. 2014 Jul 15;193(2):673-87. doi: 10.4049/jimmunol.1302058. Epub 2014 Jun 13. <a href="http://dx.doi.org/10.4049/jimmunol.1302058">Link to article on publisher's site</a>
dc.identifier.issn0022-1767 (Linking)
dc.identifier.doi10.4049/jimmunol.1302058
dc.identifier.pmid24928994
dc.identifier.urihttp://hdl.handle.net/20.500.14038/33399
dc.description.abstractT cell development in the thymus produces multiple lineages of cells, including innate T cells. Studies in mice harboring alterations in TCR signaling proteins or transcriptional regulators have revealed an expanded population of CD4(+) innate T cells in the thymus that produce IL-4 and express the transcription factor promyelocytic leukemia zinc finger (PLZF). In these mice, IL-4 produced by the CD4(+)PLZF(+) T cell population leads to the conversion of conventional CD8(+) thymocytes into innate CD8(+) T cells resembling memory T cells expressing eomesodermin. The expression of PLZF, the signature invariant NKT cell transcription factor, in these innate CD4(+) T cells suggests that they might be a subset of alphabeta or gammadelta TCR(+) NKT cells or mucosal-associated invariant T (MAIT) cells. To address these possibilities, we characterized the CD4(+)PLZF(+) innate T cells in itk(-/-) mice. We show that itk(-/-) innate PLZF(+)CD4(+) T cells are not CD1d-dependent NKT cells, MR1-dependent MAIT cells, or gammadelta T cells. Furthermore, although the itk(-/-) innate PLZF(+)CD4(+) T cells express alphabeta TCRs, neither beta2-microglobulin-dependent MHC class I nor any MHC class II molecules are required for their development. In contrast to invariant NKT cells and MAIT cells, this population has a highly diverse TCRalpha-chain repertoire. Analysis of peripheral tissues indicates that itk(-/-) innate PLZF(+)CD4(+) T cells preferentially home to spleen and mesenteric lymph nodes owing to increased expression of gut-homing receptors, and that their expansion is regulated by commensal gut flora. These data support the conclusion that itk(-/-) innate PLZF(+)CD4(+) T cells are a novel subset of innate T cells.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=24928994&dopt=Abstract">Link to Article in PubMed</a>
dc.relation.urlhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4083617/
dc.subjectAnimals; Antigens, CD1d; CD4-Positive T-Lymphocytes; Cell Differentiation; *Cell Proliferation; Cells, Cultured; Flow Cytometry; Gene Expression; H-2 Antigens; Interleukin-4; Kruppel-Like Transcription Factors; Lymph Nodes; Mice; Mice, Inbred C57BL; Mice, Knockout; Protein-Tyrosine Kinases; Receptors, Antigen, T-Cell, alpha-beta; Reverse Transcriptase Polymerase Chain Reaction; Spleen; T-Lymphocyte Subsets; Thymocytes; beta 2-Microglobulin
dc.subjectImmunity
dc.titleInnate PLZF+CD4+ alphabeta T cells develop and expand in the absence of Itk
dc.typeJournal Article
dc.source.journaltitleJournal of immunology (Baltimore, Md. : 1950)
dc.source.volume193
dc.source.issue2
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/gsbs_sp/1924
dc.identifier.contextkey7622776
html.description.abstract<p>T cell development in the thymus produces multiple lineages of cells, including innate T cells. Studies in mice harboring alterations in TCR signaling proteins or transcriptional regulators have revealed an expanded population of CD4(+) innate T cells in the thymus that produce IL-4 and express the transcription factor promyelocytic leukemia zinc finger (PLZF). In these mice, IL-4 produced by the CD4(+)PLZF(+) T cell population leads to the conversion of conventional CD8(+) thymocytes into innate CD8(+) T cells resembling memory T cells expressing eomesodermin. The expression of PLZF, the signature invariant NKT cell transcription factor, in these innate CD4(+) T cells suggests that they might be a subset of alphabeta or gammadelta TCR(+) NKT cells or mucosal-associated invariant T (MAIT) cells. To address these possibilities, we characterized the CD4(+)PLZF(+) innate T cells in itk(-/-) mice. We show that itk(-/-) innate PLZF(+)CD4(+) T cells are not CD1d-dependent NKT cells, MR1-dependent MAIT cells, or gammadelta T cells. Furthermore, although the itk(-/-) innate PLZF(+)CD4(+) T cells express alphabeta TCRs, neither beta2-microglobulin-dependent MHC class I nor any MHC class II molecules are required for their development. In contrast to invariant NKT cells and MAIT cells, this population has a highly diverse TCRalpha-chain repertoire. Analysis of peripheral tissues indicates that itk(-/-) innate PLZF(+)CD4(+) T cells preferentially home to spleen and mesenteric lymph nodes owing to increased expression of gut-homing receptors, and that their expansion is regulated by commensal gut flora. These data support the conclusion that itk(-/-) innate PLZF(+)CD4(+) T cells are a novel subset of innate T cells.</p>
dc.identifier.submissionpathgsbs_sp/1924
dc.contributor.departmentDepartment of Pathology
dc.source.pages673-87
dc.contributor.studentAmanda L. Prince; Levi B. Watkin; Catherine C. Yin


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