Impact of Inflammatory Cytokines on Effector and Memory CD8+ T Cells

Kim, Marie T.; Harty, John T.

doi:10.3389/fimmu.2014.00295

Cited by 133 publications

(51 citation statements)

References 40 publications

(46 reference statements)

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“…The molecular network controlling differentiation of effector and memory CD8 + T cells is complex, and cytokines have a central role in shaping it 11–15 . The critical role of IL-2 in promoting effector T cell differentiation is now accepted 16,17 ; however, published results showing that IL-2 was both required and dispensable for effector or memory differentiation 26,44–46 are difficult to reconcile and are probably due to the pleiotropic nature of IL-2.…”

Section: Discussionmentioning

confidence: 99%

“…Cytokines, in particular those that signal through the common γ-chain, such as interleukin 2 (IL-2), or mediate inflammation, such as IL-12, are critical for T cell differentiation 11–15 . Strong or extended IL-2 signaling drives CD8 + T cells to differentiate into effector cells, whereas weak or limited IL-2 signaling promotes their development into memory cells 16,17 .…”

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confidence: 99%

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A molecular threshold for effector CD8+ T cell differentiation controlled by transcription factors Blimp-1 and T-bet

et al. 2016

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T cell responses are guided by cytokines that induce transcriptional regulators, which ultimately control differentiation of effector and memory T cells. However, it is unknown how the activities of these molecular regulators are coordinated and integrated during the differentiation process. Using genetic approaches and transcriptional profiling of antigen-specific CD8+ T cells, we reveal a common program of effector differentiation that is regulated by IL-2 and IL-12 signaling and the combined activities of the transcriptional regulators Blimp-1 and T-bet. The loss of both T-bet and Blimp-1 leads to abrogated cytotoxic function and ectopic IL-17 production in CD8+ T cells. Overall, our data reveal two major overlapping pathways of effector differentiation governed by the availability of Blimp-1 and T-bet and suggest a model for cytokine-induced transcriptional changes that combine, quantitatively and qualitatively, to promote robust effector CD8+ T cell differentiation.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

A molecular threshold for effector CD8+ T cell differentiation controlled by transcription factors Blimp-1 and T-bet

et al. 2016

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“…The increased production of IL-2 and decreased production of IL-10 have been associated with beneficial effects on Brucella infections in mice (27). The proinflammatory cytokine IL-15 is a cell surface-associated cytokine that functions to upregulate lectin expression in inflamed tissue, maintain memory CD8 T cells, and induce the differentiation of natural killer cells (28,29).…”

Section: Discussionmentioning

confidence: 99%

Immune Responses of Bison and Efficacy after Booster Vaccination with Brucella abortus Strain RB51

Olsen¹,

McGill²,

Sacco³

et al. 2015

Clin. Vaccine Immunol.

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A lthough Brucella abortus can infect other mammalian species, cattle are the preferred host for this species of Brucella. As humans are effectively dead-end hosts, in that brucellosis is essentially not transmitted between people, the maintenance of disease in animal hosts is the source of human infection. For that reason, many industrialized countries have invested heavily in brucellosis control programs in livestock due to public health benefits from the reductions in disease prevalence in animal reservoirs. In the United States, it was estimated in 2000 that approximately 11 billion dollars had been spent in efforts to eradicate brucellosis from cattle. This investment was rewarded in 2008 by the announcement from the U.S. Department of Agriculture that for the first time in the United States, all 50 states were simultaneously free of cattle brucellosis. Despite the eradication of B. abortus from domestic livestock, the persistence of B. abortus infection in freeranging bison and elk at Yellowstone National Park and the surrounding areas remains a concern for the reintroduction of brucellosis to cattle.Previous studies have demonstrated that bison are more susceptible to infection with B. abortus than are cattle, and a single vaccination with B. abortus strain RB51 is effective in reducing the incidence of abortion and infection in bison after experimental challenge (1, 2). In a previous study with a small number of bison, we (3) demonstrated that booster vaccination with RB51 at a 13-month interval increased protection against experimental challenge compared to that provided by a single RB51 vaccination administered during calfhood. In the study reported here, we expand on the previous booster vaccination study with greater experimental units and more extensive bacteriologic and immunologic characterization. MATERIALS AND METHODSB. abortus cultures. For the immunologic assays, RB51 suspensions (1 ϫ 10 12 CFU/ml) were inactivated by gamma irradiation (1.4 ϫ 10 6 rads), washed in 0.15 M sodium chloride (saline), and stored at Ϫ70°C.Animals and inoculation. Eight-to 11-month-old bison heifers were obtained from a brucellosis-free herd. After acclimation, the bison were randomly assigned to receive either saline (control; n ϭ 7) or a single intramuscular vaccination with RB51 (n ϭ 24). Some of the vaccinated bison (n ϭ 16) were randomly selected for booster vaccination with RB51 at 11 months after the initial vaccination.A commercial RB51 vaccine was obtained in lyophilized form (Colorado Serum Company, Denver, CO) and diluted in accordance with the manufacturer's recommendations. All hand inoculations were of 2 ml in volume and administered intramuscularly in the cervical region drained by the superficial cervical lymph node. Following vaccination, the concen-

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“…Their receptors signal through Janus kinases (JAKs) and STATs to regulate the dynamic expression of transcription factors that control effector and memory differentiation 109,110 (FIG. 2).…”

Section: Cytokine Signals Shape Metabolic Functionmentioning

confidence: 99%

Synchronizing transcriptional control of T cell metabolism and function

2015

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During an immune response, cytokines and transcription factors regulate the differentiation and function of effector and memory T cells. At the same time, T cell metabolism undergoes dynamic and differentiation-stage-specific changes that are required for initial T cell activation, rapid proliferation and the acquisition of effector functions. Similarly, during the resolution of an immune response, metabolic regulation is crucial for restraining inflammatory responses and promoting peripheral tolerance, and it is required for the long-term maintenance of memory T cells. T cell receptor (TCR)-induced transcription factors, in particular MYC and interferon-regulatory factor 4 (IRF4), cooperate with canonical nutrient-sensing pathways to integrate antigen-specific and metabolic signals to appropriately modulate adaptive immune responses. In this Review, we focus on the emerging evidence that T cell differentiation and metabolism are closely linked and synchronized by immune cell-specific cytokines and transcription factors that are induced by TCR signalling.

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Impact of Inflammatory Cytokines on Effector and Memory CD8+ T Cells

Cited by 133 publications

References 40 publications

A molecular threshold for effector CD8+ T cell differentiation controlled by transcription factors Blimp-1 and T-bet

A molecular threshold for effector CD8+ T cell differentiation controlled by transcription factors Blimp-1 and T-bet

Immune Responses of Bison and Efficacy after Booster Vaccination with Brucella abortus Strain RB51

Synchronizing transcriptional control of T cell metabolism and function

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