Cytotoxic T‐lymphocyte antigen 4 blockade augments the T‐cell response primed by attenuated <i>Listeria monocytogenes</i> resulting in more rapid clearance of virulent bacterial challenge

Rowe, Jared H.; Johanns, Tanner M.; Ertelt, James M.; Lai, Joseph C.; Way, Sing Sing

doi:10.1111/j.1365-2567.2008.03001.x

Cited by 13 publications

(11 citation statements)

References 34 publications

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“…This is in accordance with a recent study reporting that CTLA4-Ig efficiency decreased in increasingly matured human T cells when stimulated with a CMV peptide or alloantigens (30). Collectively, our results suggest that human memory T cell reactivation in vitro is still CD28-dependent but tightly controlled by CTLA-4 and/or PD-L1 coinhibitory signals as described in mouse models of candida or Listeria monocytogenes infection (31,32).…”

Section: Discussionsupporting

confidence: 81%

Selective CD28 Antagonist Blunts Memory Immune Responses and Promotes Long-Term Control of Skin Inflammation in Nonhuman Primates

Poirier

Chevalier

Mary

et al. 2016

The Journal of Immunology

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Novel therapies that specifically target activation and expansion of pathogenic immune cell subsets responsible for autoimmune attacks are needed to confer long-term remission. Pathogenic cells in autoimmunity include memory T lymphocytes that are long-lived and present rapid recall effector functions with reduced activation requirements. Whereas the CD28 costimulation pathway predominantly controls priming of naive T cells and hence generation of adaptive memory cells, the roles of CD28 costimulation on established memory T lymphocytes and the recall of memory responses remain controversial. In contrast to CD80/86 antagonists (CTLA4-Ig), selective CD28 antagonists blunt T cell costimulation while sparing CTLA-4 and PD-L1–dependent coinhibitory signals. Using a new selective CD28 antagonist, we showed that Ag-specific reactivation of human memory T lymphocytes was prevented. Selective CD28 blockade controlled both cellular and humoral memory recall in nonhuman primates and induced long-term Ag-specific unresponsiveness in a memory T cell–mediated inflammatory skin model. No modification of memory T lymphocytes subsets or numbers was observed in the periphery, and importantly no significant reactivation of quiescent viruses was noticed. These findings indicate that pathogenic memory T cell responses are controlled by both CD28 and CTLA-4/PD-L1 cosignals in vivo and that selectively targeting CD28 would help to promote remission of autoimmune diseases and control chronic inflammation.

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Section: Discussionsupporting

confidence: 81%

Selective CD28 Antagonist Blunts Memory Immune Responses and Promotes Long-Term Control of Skin Inflammation in Nonhuman Primates

Poirier

Chevalier

Mary

et al. 2016

The Journal of Immunology

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“…Previous reports showed augmented endogenous CD4 + T‐cell, CD8 + T‐cell, or memory CD8 + T‐cell immunity against LM after the administration of anti‐CTLA‐4 antibody , which resulted in increased numbers of IFN‐γ‐ or IFN‐γ/TNF‐α‐secreting T cells. To investigate the efficiency and the phenotype stability of predifferentiated CTLA‐4 +/+ and CTLA‐4 −/− Tc17 cells, we compared the ability of these adoptively transferred Tc17‐cell populations to provide immunity against a high‐titer infection of OVA 257–264 ‐transgenic LM.…”

Section: Resultsmentioning

confidence: 94%

“…B), whereas CTLA‐4 −/− Tc17 cells significantly improved the ability to clear LM. Usually, this LM model has been used to test Tc1‐type immunity , which it does in our situation indirectly as well. Consistent with our in vitro findings (Fig.…”

Section: Discussionmentioning

confidence: 99%

CTLA‐4 (CD152) enhances the Tc17 differentiation program

et al. 2014

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Although CD8 + T cells that produce IL-17 (Tc17 cells) have been linked to host defense, Tc17 cells show reduced cytotoxic activity, which is the characteristic function of CD8Eur. J. Immunol. 2014Immunol. . 44: 2139Immunol. -2152 Introduction Upon activation, CD8 + T cells are able to differentiate not only into IFN-γ-producing cells (Tc1) but also into IL-17-producing effector CD8 + cells (Tc17 cells) under appropriate conditions. While Tc1 cells show massive IFN-γ production and granzyme B-and perforin-mediated target-cell lysis, Tc17 cells express high levels of IL-17, low IFN-γ, and demonstrate a noncytotoxic phenotype lacking granzyme B expression [1][2][3]. So far, Tc17 cells have been shown to provide host immunity against viral infections such as influenza and vaccinia virus [4,5] as well as anti-tumor immunity in mice [6][7][8]. Surprisingly, adoptively transferred Tc17 cells show microenvironment-dependent lineage plasticity and convert toward a Tc1-like phenotype. Consequently, most of the observed Tc17 functionality in vivo is IFN-γ dependent [6][7][8][9]. Yet it remains controversial whether the IFN-γ + or the IL-17 + /IFN-γ + Tc17 subfraction of converted Tc17 cells is most efficient. While some reports showed that IL-17/IFN-γ-double-positive Tc17 cells lack lytic activity [9], other reports assigned strong in vivo activity to these double producers [10]. The IL-17 + /IFN-γ + producers are induced by , whereas IL-23 and IL-21 are able to stabilize the IL-17 producing phenotype [2,13] and counteract IL-12-mediated signaling [14]. Nevertheless, apart from the cytokine pattern, certain Tc17-related characteristics such as increased persistence or survival in vivo are retained by the converted Tc17 cells, which clearly distinguish them from conventional Tc1 cells [9,15]. With this in mind, factors that determine Tc17 lineage plasticity or stability, though not fully understood so far, remain of major interest. The Tc1-as well as the Tc17 transcriptional program forms a positive feedback loop and each inhibits the opposing program. T-bet and Eomes are the two master transcription factors of the Tc1 program, whereas RORγt is the master transcription factor for the Tc17 program [1,16]. Interestingly, Tc1 cells lacking Eomes and T-bet show Tc17 characteristics, such as high levels of IL-17 and RORγt expression with reduced IFN-γ, granzyme B, and perforin production, leading to an inappropriate antiviral host defense [17]. This implies that Tc17 differentiation is the default pathway in the absence of the Tc1 differentiation program. With regard to the inhibition of opposing programs, Tc1-inducing transcription factors, as well as the master Tc1 cytokine IFN-γ, are crucial inhibitors of the Tc17 program and its master transcription factor RORγt.CTLA-4 (CD152) is a glycoprotein of the Ig-superfamily that is expressed on the cell surface of T cells. It has homology to the primary costimulatory molecule CD28 and binds the same ligands-CD80 and CD86. It is well known that CTLA-4 abrogates T-cell responses vi...

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“…6 d). 29 In the liver, all groups had higher expression of CTLA-4 than naive mice, with LMD reaching statistically significant expression on day 14 ( P < 0.05) (Fig. 6 d).…”

Section: Resultsmentioning

confidence: 84%

“… 30 , 36 Rowe et al showed that blockade of CTLA-4 led to augmented antigen-specific CD4 + and CD8 + T-cell responses directed toward an attenuated strain of L. monocytogenes during primary infection. 29 Pedicord et al reported that a single dose of anti-CTLA-4 antibody, when administered with Listeria monocytogenes, enhanced bacterial clearance upon rechallenge as a result of an increase in the production of effector memory T cells. 37 Conceivably, the blockade of CTLA-4 could increase antigen-specific responses to tumor-associated antigens delivered by L. monocytogenes allowing for stronger initial antitumor responses or for smaller doses of antigen expressing L. monocytogenes to be administered, thus increasing the safety profile with the use of this bacterium.…”

Section: Discussionmentioning

confidence: 99%

Tumor-Associated Antigen Expressing Listeria monocytogenes Induces Effective Primary and Memory T-Cell Responses Against Hepatic Colorectal Cancer Metastases

et al. 2011

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PurposeDespite advances in therapy for the treatment of metastatic colorectal cancer, many patients die of hepatic disease. Current immunotherapeutic strategies are likely limited by inhibitory signals from the tumor. To successfully eliminate tumor deposits within an organ, an appropriate immunologic milieu to amplify antitumor responses must be developed.MethodsWe used a murine model utilizing the CT26 colon cancer cell line to analyze primary and memory tumor-specific T-cell responses induced by an attenuated actin A and internalin B deleted immunodominant tumor-associated antigen expressing strain of Listeria monocytogenes for the treatment of metastatic colorectal cancer.ResultsTreatment of mice bearing established hepatic metastases with this L. monocytogenes strain led to the generation of a strong initial tumor-specific cytotoxic CD8+ T-cell response that successfully treated 90% of animals. Tumor antigen-specific central and effector memory T cells were also generated and protected against tumor rechallenge. These cell populations, when measured before and after tumor rechallenge, showed a marked expansion of antigen-specific effector CD8+ effector memory T cells. This strain of L. monocytogenes was able to down-modulate the expression of the immune checkpoint molecule, PD-1, within the tumor microenvironment but had variable effects on CTLA-4 expression.ConclusionsThis L. monocytogenes strain generated a highly effective antitumor T-cell response, providing a basis for the development of this vaccine platform in patients with liver metastases.Electronic supplementary materialThe online version of this article (doi:10.1245/s10434-011-2037-0) contains supplementary material, which is available to authorized users.

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Cytotoxic T‐lymphocyte antigen 4 blockade augments the T‐cell response primed by attenuated Listeria monocytogenes resulting in more rapid clearance of virulent bacterial challenge

Cited by 13 publications

References 34 publications

Selective CD28 Antagonist Blunts Memory Immune Responses and Promotes Long-Term Control of Skin Inflammation in Nonhuman Primates

Selective CD28 Antagonist Blunts Memory Immune Responses and Promotes Long-Term Control of Skin Inflammation in Nonhuman Primates

CTLA‐4 (CD152) enhances the Tc17 differentiation program

Tumor-Associated Antigen Expressing Listeria monocytogenes Induces Effective Primary and Memory T-Cell Responses Against Hepatic Colorectal Cancer Metastases

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