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J Adam Best,
David A Blair,
Jamie Knell,
Edward Yang,
Viveka Mayya,
Andrew Doedens,
Michael L Dustin,
Ananda W Goldrath,
Paul Monach,
Susan A Shinton, [......],
Tata Nageswara Rao,
Amy Wagers, Tracy Heng,
Michio Painter,
Jeffrey Ericson,
Scott Davis,
Ayla Ergun,
Michael Mingueneau,
Diane Mathis,
Christophe Benoist
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ABSTRACT: After infection, many factors coordinate the population expansion and differentiation of CD8(+) effector and memory T cells. Using data of unparalleled breadth from the Immunological Genome Project, we analyzed the CD8(+) T cell transcriptome throughout infection to establish gene-expression signatures and identify putative transcriptional regulators. Notably, we found that the expression of key gene signatures can be used to predict the memory-precursor potential of CD8(+) effector cells. Long-lived memory CD8(+) cells ultimately expressed a small subset of genes shared by natural killer T and γδ T cells. Although distinct inflammatory milieu and T cell precursor frequencies influenced the differentiation of CD8(+) effector and memory populations, core transcriptional signatures were regulated similarly, whether polyclonal or transgenic, and whether responding to bacterial or viral model pathogens. Our results provide insights into the transcriptional regulation that influence memory formation and CD8(+) T cell immunity.
Nature Immunology 02/2013; · 26.01 Impact Factor
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Nadia R Cohen,
Patrick J Brennan,
Tal Shay,
Gerald F Watts,
Manfred Brigl,
Joonsoo Kang,
Michael B Brenner,
Paul Monach,
Susan A Shinton,
Richard R Hardy, [......],
Tata Nageswara Rao,
Amy Wagers, Tracy Heng,
Michio Painter,
Jeffrey Ericson,
Scott Davis,
Ayla Ergun,
Michael Mingueneau,
Diane Mathis,
Christophe Benoist
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ABSTRACT: Invariant natural killer T cells (iNKT cells) are innate-like T lymphocytes that act as critical regulators of the immune response. To better characterize this population, we profiled gene expression in iNKT cells during ontogeny and in peripheral subsets as part of the Immunological Genome Project. High-resolution comparative transcriptional analyses defined developmental and subset-specific programs of gene expression by iNKT cells. In addition, we found that iNKT cells shared an extensive transcriptional program with NK cells, similar in magnitude to that shared with major histocompatibility complex (MHC)-restricted T cells. Notably, the program shared by NK cells and iNKT cells also operated constitutively in γδ T cells and in adaptive T cells after activation. Together our findings highlight a core effector program regulated distinctly in innate and adaptive lymphocytes.
Nature Immunology 12/2012; · 26.01 Impact Factor
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Emmanuel L Gautier,
Tal Shay,
Jennifer Miller,
Melanie Greter,
Claudia Jakubzick,
Stoyan Ivanov,
Julie Helft,
Andrew Chow,
Kutlu G Elpek,
Simon Gordonov, [......],
Joseph C Sun,
Charlie C Kim,
Lewis L Lanier, Tracy Heng,
Taras Kreslavsky,
Michio Painter,
Jeffrey Ericson,
Scott Davis,
Diane Mathis,
Christophe Benoist
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ABSTRACT: We assessed gene expression in tissue macrophages from various mouse organs. The diversity in gene expression among different populations of macrophages was considerable. Only a few hundred mRNA transcripts were selectively expressed by macrophages rather than dendritic cells, and many of these were not present in all macrophages. Nonetheless, well-characterized surface markers, including MerTK and FcγR1 (CD64), along with a cluster of previously unidentified transcripts, were distinctly and universally associated with mature tissue macrophages. TCEF3, C/EBP-α, Bach1 and CREG-1 were among the transcriptional regulators predicted to regulate these core macrophage-associated genes. The mRNA encoding other transcription factors, such as Gata6, was associated with single macrophage populations. We further identified how these transcripts and the proteins they encode facilitated distinguishing macrophages from dendritic cells.
Nature Immunology 09/2012; 13(11):1118-1128. · 26.01 Impact Factor
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Natalie A Bezman,
Charles C Kim,
Joseph C Sun,
Gundula Min-Oo,
Deborah W Hendricks,
Yosuke Kamimura,
J Adam Best,
Ananda W Goldrath,
Lewis L Lanier,
Emmanuel L Gautier, [......],
Richard R Hardy,
Paul Monach,
Charlie C Kim, Tracy Heng,
Taras Kreslavsky,
Michio Painter,
Jeffrey Ericson,
Scott Davis,
Diane Mathis,
Christophe Benoist
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ABSTRACT: Using whole-genome microarray data sets of the Immunological Genome Project, we demonstrate a closer transcriptional relationship between NK cells and T cells than between any other leukocytes, distinguished by their shared expression of genes encoding molecules with similar signaling functions. Whereas resting NK cells are known to share expression of a few genes with cytotoxic CD8(+) T cells, our transcriptome-wide analysis demonstrates that the commonalities extend to hundreds of genes, many encoding molecules with unknown functions. Resting NK cells demonstrate a 'preprimed' state compared with naive T cells, which allows NK cells to respond more rapidly to viral infection. Collectively, our data provide a global context for known and previously unknown molecular aspects of NK cell identity and function by delineating the genome-wide repertoire of gene expression of NK cells in various states.
Nature Immunology 08/2011; 13(10):1000-1009. · 26.01 Impact Factor
