EBV-Induced Human CD8+ NKT Cells Synergise CD4+ NKT Cells Suppressing EBV-Associated Tumours Upon Induction of Th1-Bias

Xiao, Wei; Li, Li; Zhou, Rui; Xiao, Ran; Wang, Yujuan; Xiang, Jianbin; Wu, Minxian; Wang, Lan; Huang, Wei; Zheng, Xia; Xinti, Tan; Chen, Lang; Xiong, Tingting; Xiong, Jie; Jin, Youxin; Jinquan, Tan; He, Yong

doi:10.1038/cmi.2009.48

Cited by 12 publications

(12 citation statements)

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“…This shift or switch between Th1 and Th2 cytokines produced by NKT cells is possibly a requirement of development, or even a byproduct of maturation. Yuling et al have reported that EBV-induced CD8 + NKT cells are prone to express more IFN-γ under the stimulation of α-GalCer, whereas CD4 -NKT cells bias towards secretion of IL-4 and IL-10, which is in accord with the finding that CD4 + NKT cells have the superior capacity to produce Th2 cytokines over CD4 -NKT cells including CD8 + NKT cells in humans, which preferentially induce Th1 cytokines production [7,8] . This provides an explanation for separate immunoregulatory responses of individual subset of NKT cells, which could significantly affect the direction of an immune reaction.…”

Section: Polarization Of Th1 and Th2 Cytokines In Nkt Cellssupporting

confidence: 79%

“…Recently, several endogenous mammalian self lipids have been defined as CD1d ligands recognized by NKT cells, including isoglobotrihexosylceramide (iGb3) and other phosphatidyl inositol compounds, but these are still controversial and need to be further confirmed [5,6] . However, we found that the infection of Epstein-Barr virus (EBV), but not human T-cell leukemia virus type I (HTLV-1), can profoundly promote EBV-associated CD8 + NKT cell development in humans and human-thymus/liver-SCID (hu-thym/liv-SCID) chimeras, suggesting whether other types of antigen are involved in differentiation and maturation of NKT cells is still unknown [7][8][9] .…”

Section: Introductionmentioning

confidence: 99%

“…Th1 cytokines from activated NKT cells responded to α-GalCer promote cell-mediated cytotoxity and maturation of DCs, which are involved in the development of cognate T cell responses [83] . The EBV-induced human CD8 + NKT cells cooperated with syngenic CD3 + T cells to kill or suppress EBV-associated tumors upon induction of Th1-bias, and the synergy is enhanced by addition of CD4 + NKT cells, which secrete high levels of IL-2 to maintain the transferred cells [7,8] . Thymic CD8 + NKT cells induced by EBV could significantly drive CD3 + T cells to produce high levels of IFN-γ combined with autocrine Th1 cytokines to resist tumors, which is consistent with IFN-γ-mediated anti-tumor activity of NKT cells on α-GalCer stimulation [84,85] .…”

Section: Nkt Cells In Tumor Immunitymentioning

confidence: 99%

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Type I natural killer T cells: naturally born for fighting

et al. 2010

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Type І natural killer T cells (NKT cells), a subset of CD1d-restricted T cells with invariant Vαβ TCR, are characterized by prompt production of large amounts of Th1 and/or Th2 cytokines upon primary stimulation through the TCR complex. The rapid release of cytokines implies that type І NKT cells may play a critical role in modulating the upcoming immune responses, such as anti-tumor response, protection against infection, and autoimmunity. As a bridge between innate and adaptive immunity, type І NKT cells differentiate and mature upon stimulations to achieve and maintain a homeostasis. Orchestrating with other arms of adaptive immunity, type І NKT cells show strong cytotoxic effects in response to various tumors in a direct and/or indirect manner(s). This review will focus primarily on type І NKT cell development, homeostasis, and effector functions, especially in anti-tumor immunity, and followed by their potential applications in treatment of cancers.

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Section: Polarization Of Th1 and Th2 Cytokines In Nkt Cellssupporting

confidence: 79%

Section: Introductionmentioning

confidence: 99%

Section: Nkt Cells In Tumor Immunitymentioning

confidence: 99%

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Type I natural killer T cells: naturally born for fighting

et al. 2010

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“…Similarly, NKT cells were protective against L. donovani compared with the wells without NKT cells. CD8 + NKT cells synergize with CD4 + NKT cells to enhance immunity against tumour cells [50] In this experiment, NKT cells were in contact with L. donovani impregnated macrophages. However, this may not apply to VL because of the un-accessibility of CD3 + CD8 + CD56 + NKT cells at the infection site as shown by the previous results.…”

Section: Ifn-γ Fitc →mentioning

confidence: 99%

Leishmania donovani skews the CD56+ Natural Killer T cell response during human visceral leishmaniasis

et al. 2015

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“…Moreover, NK-like CD8 + T-cells from Epstein–Barr virus (EBV)-associated tumor patients are quantitatively and functionally impaired and in a human-thymus-SCID chimera model, the EBV-induced human NK-like CD8 + T-cells synergize with NK-like CD4 + T-cells suppressing EBV-associated tumors upon induction of a Th1-bias (43). Additionally, in women with human papillomavirus (HPV)-associated cervical neoplasia, there are increased levels of CD28 − , T EM , and CD16 + CD56 + CD8 + T-cells in peripheral blood, probably associated with the chronic infection with HPV (44).…”

Section: Nk-like Cd8+ T-cells In Virus Infection and Immunosenescencementioning

confidence: 99%

Adaptive Memory of Human NK-like CD8+ T-Cells to Aging, and Viral and Tumor Antigens

2016

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Human natural killer (NK)-like CD8+ T-cells are singular T-cells that express both T and NK cell markers such as CD56; their frequencies depend on their differentiation and activation during their lifetime. There is evidence of the presence of these innate CD8+ T-cells in the human umbilical cord, highlighting the necessity of investigating whether the NK-like CD8+ T-cells arise in the early stages of life (gestation). Based on the presence of cell surface markers, these cells have also been referred to as CD8+KIR+ T-cells, innate CD8+ T-cells, CD8+CD28−KIR+ T-cells or NKT-like CD8+CD56+ cells. However, the functional and co-signaling significance of these NK cell receptors on NK-like CD8+ T-cells is less clear. Also, the diverse array of costimulatory and co-inhibitory receptors are spatially and temporally regulated and may have distinct overlapping functions on NK-like CD8+ T-cell priming, activation, differentiation, and memory responses associated with different cell phenotypes. Currently, there is no consensus regarding the functional properties and phenotypic characterization of human NK-like CD8+ T-cells. Environmental factors, such as aging, autoimmunity, inflammation, viral antigen re-exposure, or the presence of persistent tumor antigens have been shown to allow differentiation (“adaptation”) of the NK-like CD8+ T-cells; the elucidation of this differentiation process and a greater understanding of the characteristics of these cells could be important for their eventual in potential therapeutic applications aimed at improving protective immunity. This review will attempt to elucidate an understanding of the characteristics of these cells with the goal toward their eventual use in potential therapeutic applications aimed at improving protective immunity.

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EBV-Induced Human CD8+ NKT Cells Synergise CD4+ NKT Cells Suppressing EBV-Associated Tumours Upon Induction of Th1-Bias

Cited by 12 publications

References 27 publications

Type I natural killer T cells: naturally born for fighting

Type I natural killer T cells: naturally born for fighting

Leishmania donovani skews the CD56+ Natural Killer T cell response during human visceral leishmaniasis

Adaptive Memory of Human NK-like CD8+ T-Cells to Aging, and Viral and Tumor Antigens

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