Effect of IL-4 on the Development and Function of Memory-like CD8 T Cells in the Peripheral Lymphoid Tissues

Park, Hi Jung; Lee, Ara; Lee, Jae Il; Park, Seong Hoe; Ha, Sang‐Jun; Jung, Kyeong Cheon

doi:10.4110/in.2016.16.2.126

Cited by 14 publications

(10 citation statements)

References 19 publications

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“…In support of our conclusion, it has been reported that the administration of IL-4/anti-IL-4 antibody complexes into naïve B6 mice as well as OT-I TCR transgenic mice could induce the generation of memory-like CD8 T cell in the periphery. 36 It is conceivable that IL-15—which is also critical for CD8 T VM cell development and can induce the expansion of CD8 T VM cells in vivo 25,26,37 — could partially compensate the absence of IL-4 or IL-4Rα, particularly when diverse cellular subsets are engaged during complex immune responses to infections (Figure 2d,e). However, it is less clear how this occurs upon the selective activation of iNKT cells by αGalCer (Figure 2c).…”

Section: Discussionmentioning

confidence: 99%

Virtual memory CD8 T cells expanded by helminth infection confer broad protection against bacterial infection

et al. 2019

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Epidemiological data and animal studies suggest that helminth infection exerts potent immunomodulatory effects that dampen host immunity against unrelated pathogens. Despite this notion, we unexpectedly discovered that prior helminth infection resulted in enhanced protection against subsequent systemic and enteric bacterial infection. A population of virtual memory CD8 T (CD8 T VM ) cells underwent marked expansion upon infection with the helminth Heligmosomoides polygurus by an IL-4-regulated, antigen-independent mechanism. CD8 T VM cells disseminated to secondary lymphoid organs and established a major population of the systemic CD8 T cell pool. IL-4 production elicited by protein immunization or selective activation of natural killer T cells also results in the expansion of CD8 T VM cells. Notably, CD8 T VM cells expanded by helminth infection are sufficient to transfer innate non-cognate protection against bacteria to naïve animals. This innate non-cognate “collateral protection” mediated byCD8 T VM might provide parasitized animals an advantage against subsequent unrelated infections, and represents a potential novel strategy for vaccination.

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Section: Discussionmentioning

confidence: 99%

Virtual memory CD8 T cells expanded by helminth infection confer broad protection against bacterial infection

et al. 2019

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“…Recently, Park et al reported that some T cells with a memory-like phenotype in the thymus respond immediately to antigenic stimulation [ 42 ]. These T cells include NKT cells, PLZF + T-T CD4 (or T-CD4) T cells, H2-M3-specific T cells, mucosal-associated invariant T (MAIT) cells, CD8 αα + intraepithelial T cells, Eomes + natural Th1 cells, and innate CD8 T cells expressing Eomes [ 42 – 44 ]. Jacomet et al reported strong evidence for the presence of innate-like CD8 T cells in humans and showed that they are Eomes positive [ 45 ].…”

Section: Discussionmentioning

confidence: 99%

CD4^hiCD8^lowDouble-Positive T Cells Are Associated with Graft Rejection in a Nonhuman Primate Model of Islet Transplantation

Choi

Park

et al. 2018

Journal of Immunology Research

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Peripheral CD4/CD8 double-positive (DP) T cells are associated with autoimmune disorders, cancer, and viral infection. However, the relationship between organ transplantation and DP T cells is unclear. Here, we examined the functional characteristics of peripheral DP T cells and analyzed their significance with respect to islet graft rejection in a nonhuman primate model of islet transplantation. DP T cells were functionally equivalent to conventional CD4 and CD8 T cells in terms of helper and cytotoxic activity, respectively. DP T cells expressed high levels of CXCR5 and PD-1 and secreted IFN-γ, IL-4, and IL-21 in amounts equivalent to those secreted by CD4 or CD8 T cells; also, they produced large amounts of granzyme B and perforin. In addition, under steady-state conditions, DP T cells expressed eomesodermin (Eomes) and promyelocytic leukemia zinc finger (PLZF) proteins, both of which act as transcription factors in innate/memory-like T cells. The number of peripheral DP T cells in the islet transplantation model was high in the group that experienced graft rejection; this was not the case in the long-term survival group. Interestingly, numbers of effector memory T cells (TEM) within the DP T cell population increased significantly during islet graft rejection, as did those of TEM within the cytotoxic CD8 T cells. Furthermore, the most conspicuous of which was the increase of CD4hiCD8low T cell subpopulation at that point. Taken together, the data suggest that peripheral DP T cells showing an innate/memory-like phenotype have both helper and cytotoxic activity in vitro and that they may act as a novel biomarker for graft rejection after islet transplantation.

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“…Conversion of a naïve CD8 + T cells to the innate phenotype may also occur in SLO in the presence of IL-4 as reported by others[13, 18, 57, 58]. Moreover, it has been demonstrated that even conventional αβ memory CD8 T cells are able to exert innate-like functions in response to heterologous challenge (e.g.…”

Section: Discussionmentioning

confidence: 60%

“…Over the years, innate CD8 + T cells have been further characterized based on their phenotypic and functional properties[15]. During their thymic maturation, innate CD8 + T cells up-regulate CD44 and CD122 expression and also acquire high cytotoxic and cytokine production capacities, while conventional memory T cells adopt these characteristic in secondary lymphoid organs (SLO)[16–18]. Other features of innate CD8 + T cells include 1: they exert their cytotoxic activity in an Ag-independent manner, 2: they highly depend upon IL-15 for proliferation and 3: they are able to rapidly produce interferon-gamma (IFNγ) when stimulated by IL-12 and IL-18 as response similar to that of NK cells[19–21].…”

Section: Introductionmentioning

confidence: 99%

Thymic expression of IL-4 and IL-15 after systemic inflammatory or infectious Th1 disease processes induce the acquisition of "innate" characteristics during CD8+ T cell development

et al. 2019

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Innate CD8+ T cells express a memory-like phenotype and demonstrate a strong cytotoxic capacity that is critical during the early phase of the host response to certain bacterial and viral infections. These cells arise in the thymus and depend on IL-4 and IL-15 for their development. Even though innate CD8+ T cells exist in the thymus of WT mice in low numbers, they are highly enriched in KO mice that lack certain kinases, leading to an increase in IL-4 production by thymic NKT cells. Our work describes that in C57BL/6 WT mice undergoing a Th1 biased infectious disease, the thymus experiences an enrichment of single positive CD8 (SP8) thymocytes that share all the established phenotypical and functional characteristics of innate CD8+ T cells. Moreover, through in vivo experiments, we demonstrate a significant increase in survival and a lower parasitemia in mice adoptively transferred with SP8 thymocytes from OT I—T. cruzi-infected mice, demonstrating that innate CD8+ thymocytes are able to protect against a lethal T. cruzi infection in an Ag-independent manner. Interestingly, we obtained similar results when using thymocytes from systemic IL-12 + IL-18-treated mice. This data indicates that cytokines triggered during the acute stage of a Th1 infectious process induce thymic production of IL-4 along with IL-15 expression resulting in an adequate niche for development of innate CD8+ T cells as early as the double positive (DP) stage. Our data demonstrate that the thymus can sense systemic inflammatory situations and alter its conventional CD8 developmental pathway when a rapid innate immune response is required to control different types of pathogens.

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Effect of IL-4 on the Development and Function of Memory-like CD8 T Cells in the Peripheral Lymphoid Tissues

Cited by 14 publications

References 19 publications

Virtual memory CD8 T cells expanded by helminth infection confer broad protection against bacterial infection

Virtual memory CD8 T cells expanded by helminth infection confer broad protection against bacterial infection

CD4^hiCD8^lowDouble-Positive T Cells Are Associated with Graft Rejection in a Nonhuman Primate Model of Islet Transplantation

Thymic expression of IL-4 and IL-15 after systemic inflammatory or infectious Th1 disease processes induce the acquisition of "innate" characteristics during CD8+ T cell development

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Effect of IL-4 on the Development and Function of Memory-like CD8 T Cells in the Peripheral Lymphoid Tissues

Cited by 14 publications

References 19 publications

Virtual memory CD8 T cells expanded by helminth infection confer broad protection against bacterial infection

Virtual memory CD8 T cells expanded by helminth infection confer broad protection against bacterial infection

CD4hiCD8lowDouble-Positive T Cells Are Associated with Graft Rejection in a Nonhuman Primate Model of Islet Transplantation

Thymic expression of IL-4 and IL-15 after systemic inflammatory or infectious Th1 disease processes induce the acquisition of "innate" characteristics during CD8+ T cell development

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CD4^hiCD8^lowDouble-Positive T Cells Are Associated with Graft Rejection in a Nonhuman Primate Model of Islet Transplantation