Anomalous Type 17 Response to Viral Infection by CD8
            <sup>+</sup>
            T Cells Lacking T-bet and Eomesodermin

Intlekofer, Andrew M.; Banerjee, Arnob; Takemoto, Naofumi; Gordon, Scott M.; DeJong, Caitlin S.; Shin, Haina; Hunter, Christopher A.; Wherry, E. John; Lindsten, Tullia; Reiner, Steven L.

doi:10.1126/science.1159806

Cited by 356 publications

(414 citation statements)

References 24 publications

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“…According to redundant functions between Eomes and T-bet, we did not observe differences in the accumulation of Eomes-deficient Th1 cells under inflammatory conditions or under steady state, despite the fact that the majority of Eomes + WT cells under those conditions were active producers of IFN-g. Therefore, we concluded that Eomes does not play an essential nonredundant role in Th1 responses in vivo, which is in line with previous reports (21,22).…”

Section: Discussionsupporting

confidence: 80%

“…Eomes restrains the age-dependent accumulation of CD4 + Foxp3 + T cells (21). In line with levels of Eomes + CD4 + T cells being very low in young animals, we did not observe any differences in the frequencies of IFN-g-or IL-17-producing CD4 + cells in 2-mo-old mice ( Fig.…”

Section: Eomes + Cd4 + T Cells Accumulate With Agesupporting

confidence: 65%

“…Eomes has also been reported to repress the Th17 fate during CD4 + and CD8 + T cell polarization, although for the latter in a redundant way with T-bet (9,21,26). Reciprocally, the TGF-b-JNK-c-Jun signaling pathway was shown to repress Eomes during Th17 polarization (26).…”

Section: Discussionmentioning

confidence: 99%

“…Gain-and loss-of-function experiments in both CD8 + (14,21,38,59) and CD4 + (8,11,22,40) T cells have shown that Eomes promotes cytotoxicity and IFN-g production in mice and humans. However, none of these settings showed essential functions of Eomes for the induction of IFN-g, probably due to compensatory effects of the related transcription factor Tbet (21,22,57). Indeed, Eomes can be expressed by T-bet-deficient T cells and partially replace T-bet function (8,23,24,57).…”

Section: Discussionmentioning

confidence: 99%

“…Eomes is expressed in fewer CD4 + T cells compared with CD8 + T cells under steady state (19), and CD4 + T cells seem to rely more on T-bet than on Eomes for polarization (20,21). Hence, T-bet-deficient CD4 + T cells are more severely impaired in IFN-g production compared with T-bet-deficient CD8 + T cells, indicating that Eomes cannot compensate for the lack of T-bet in CD4 + T cells (20,21). Accordingly, silencing of Eomes does not impact on IFN-g production by T-bet-sufficient CD4 + T cells (22).…”

Section: T He Cd4 + T Cells Coordinate Different Types Of Immunementioning

confidence: 99%

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Eomesodermin Expression in CD4+ T Cells Restricts Peripheral Foxp3 Induction

Lupar¹,

Brack

Garnier

et al. 2015

The Journal of Immunology

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CD4+ T cells polarize into effector Th subsets characterized by signature transcription factors and cytokines. Although T-bet drives Th1 responses and represses the alternative Th2, Th17, and Foxp3+ regulatory T cell fates, the role of the T-bet–related transcription factor eomesodermin (Eomes) in CD4+ T cells is less well understood. In this study, we analyze the expression and effects of Eomes in mouse CD4+ T lymphocytes. We find that Eomes is readily expressed in activated CD4+ Th1 T cells in vivo. Eomes+ CD4+ T cells accumulated in old mice, under lymphopenic conditions in a T cell transfer model of colitis, and upon oral Ag administration. However, despite its expression, genetic deletion of Eomes in CD4+ T cells did not impact on IFN-γ production nor increase Th2 or Th17 responses. In contrast, Eomes deficiency favored the accumulation of Foxp3+ cells in old mice, after in vivo differentiation of Eomes-deficient naive CD4+ T cells, and in response to oral Ag in a cell-intrinsic way. Enforced Eomes expression during in vitro regulatory T cell induction also reduced Foxp3 transcription. Likewise, bystander Eomes-deficient CD4+ T cells were more efficient at protecting from experimental autoimmune encephalitis compared with wild-type CD4+ T cells. This enhanced capacity of Eomes-deficient CD4+ T cells to inhibit EAE in trans was associated with an enhanced frequency of Foxp3+ cells. Our data identify a novel role for Eomes in CD4+ T cells and indicate that Eomes expression may act by limiting Foxp3 induction, which may contribute to the association of EOMES to susceptibility to multiple sclerosis.

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Section: Discussionsupporting

confidence: 80%

Section: Eomes + Cd4 + T Cells Accumulate With Agesupporting

confidence: 65%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: T He Cd4 + T Cells Coordinate Different Types Of Immunementioning

confidence: 99%

See 3 more Smart Citations

Eomesodermin Expression in CD4+ T Cells Restricts Peripheral Foxp3 Induction

Lupar¹,

Brack

Garnier

et al. 2015

The Journal of Immunology

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Simultaneous, Single‐Cell Measurement of Messenger RNA, Cell Surface Proteins, and Intracellular Proteins

et al. 2016

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Nucleic acid content can be quantified by flow cytometry through the use of intercalating compounds; however, measuring the presence of specific sequences has hitherto been difficult to achieve by this methodology. The primary obstacle to detecting discrete nucleic acid sequences by flow cytometry is their low quantity and the presence of high background signals, rendering the detection of hybridized fluorescent probes challenging. Amplification of nucleic acid sequences by molecular techniques such as in situ PCR have been applied to single‐cell suspensions, but these approaches have not been easily adapted to conventional flow cytometry. An alternative strategy implements a Branched DNA technique, comprising target‐specific probes and sequentially hybridized amplification reagents, resulting in a theoretical 8,000‐ to 16,000‐fold increase in fluorescence signal amplification. The Branched DNA technique allows for the quantification of native and unmanipulated mRNA content with increased signal detection and reduced background. This procedure utilizes gentle fixation steps with low hybridization temperatures, leaving the assayed cells intact to permit their concomitant immunophenotyping. This technology has the potential to advance scientific discovery by correlating potentially small quantities of mRNA with many biological measurements at the single‐cell level. © 2016 by John Wiley & Sons, Inc.

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Pathogenic CD8⁺ T cells in multiple sclerosis

Friese

Fugger

2009

Annals of Neurology

151

123

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Traditionally, autoimmune pathogeneses have been attributed to CD4(+) T lymphocytes, as in multiple sclerosis (MS), rheumatoid arthritis, type 1 diabetes mellitus, and/or to B lymphocytes, as in myasthenia gravis and systemic lupus erythematosus. That is because their primary genetic associations are mostly with certain human leukocyte antigen class II alleles, whose gene products present antigens to CD4(+) T cells. Because few autoimmune diseases show stronger associations with major histocompatibility complex class I alleles (ankylosing spondylitis, Behçet's disease, and psoriasis), CD8(+) T cells, which interact with major histocompatibility complex class I molecules, have been largely ignored in autoimmunity research. However, a variety of findings has recently revived interest in this population, particularly in MS. First, it shows associations with major histocompatibility complex class I alleles. Second, its lesions show a predominance of CD8(+) T cells. Third, these represent effectors that can directly damage central nervous system target cells. Furthermore, several clinical trials of monoclonal antibodies specifically against CD4(+) T cells, or the polarizing cytokines on which they depend, have failed to show any therapeutic benefit in MS, unlike broader-spectrum antibodies that deplete all T cells. Here, we review the evidence that CD8(+) T cells play a role in MS pathogenesis.

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Anomalous Type 17 Response to Viral Infection by CD8 ⁺ T Cells Lacking T-bet and Eomesodermin

Cited by 356 publications

References 24 publications

Eomesodermin Expression in CD4+ T Cells Restricts Peripheral Foxp3 Induction

Eomesodermin Expression in CD4+ T Cells Restricts Peripheral Foxp3 Induction

Simultaneous, Single‐Cell Measurement of Messenger RNA, Cell Surface Proteins, and Intracellular Proteins

Pathogenic CD8⁺ T cells in multiple sclerosis

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Anomalous Type 17 Response to Viral Infection by CD8 + T Cells Lacking T-bet and Eomesodermin

Cited by 356 publications

References 24 publications

Eomesodermin Expression in CD4+ T Cells Restricts Peripheral Foxp3 Induction

Eomesodermin Expression in CD4+ T Cells Restricts Peripheral Foxp3 Induction

Simultaneous, Single‐Cell Measurement of Messenger RNA, Cell Surface Proteins, and Intracellular Proteins

Pathogenic CD8+ T cells in multiple sclerosis

Contact Info

Product

Resources

About

Anomalous Type 17 Response to Viral Infection by CD8 ⁺ T Cells Lacking T-bet and Eomesodermin

Pathogenic CD8⁺ T cells in multiple sclerosis