Comparative gene expression analysis of NKT cell subpopulations

Lin, Hsien-Chung; Nieda, Mie; Hutton, Jonathon F.; Rozenkov, Vladislav; Nicol, Andrew

doi:10.1189/jlb.0705421

Cited by 32 publications

(21 citation statements)

References 69 publications

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“…Our data show that therapeutic manipulation of iNKT cells may necessarily require the sorting of iNKT cells into functionally-distinct subsets. As well as selecting for desired effector functions, sorting of iNKT cell subsets could also allow selection of iNKT cells with distinct adhesion [46] and homing receptors [9], [42], [46], [47] that will promote optimal localization to the relevant sites.…”

Section: Discussionmentioning

confidence: 99%

Distinct and Overlapping Effector Functions of Expanded Human CD4+, CD8α+ and CD4-CD8α- Invariant Natural Killer T Cells

et al. 2011

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CD1d-restricted invariant natural killer T (iNKT) cells have diverse immune stimulatory/regulatory activities through their ability to release cytokines and to kill or transactivate other cells. Activation of iNKT cells can protect against multiple diseases in mice but clinical trials in humans have had limited impact. Clinical studies to date have targeted polyclonal mixtures of iNKT cells and we proposed that their subset compositions will influence therapeutic outcomes. We sorted and expanded iNKT cells from healthy donors and compared the phenotypes, cytotoxic activities and cytokine profiles of the CD4+, CD8α+ and CD4−CD8α− double-negative (DN) subsets. CD4+ iNKT cells expanded more readily than CD8α+ and DN iNKT cells upon mitogen stimulation. CD8α+ and DN iNKT cells most frequently expressed CD56, CD161 and NKG2D and most potently killed CD1d+ cell lines and primary leukemia cells. All iNKT subsets released Th1 (IFN-γ and TNF-α) and Th2 (IL-4, IL-5 and IL-13) cytokines. Relative amounts followed a CD8α>DN>CD4 pattern for Th1 and CD4>DN>CD8α for Th2. All iNKT subsets could simultaneously produce IFN-γ and IL-4, but single-positivity for IFN-γ or IL-4 was strikingly rare in CD4+ and CD8α+ fractions, respectively. Only CD4+ iNKT cells produced IL-9 and IL-10; DN cells released IL-17; and none produced IL-22. All iNKT subsets upregulated CD40L upon glycolipid stimulation and induced IL-10 and IL-12 secretion by dendritic cells. Thus, subset composition of iNKT cells is a major determinant of function. Use of enriched CD8α+, DN or CD4+ iNKT cells may optimally harness the immunoregulatory properties of iNKT cells for treatment of disease.

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Section: Discussionmentioning

confidence: 99%

Distinct and Overlapping Effector Functions of Expanded Human CD4+, CD8α+ and CD4-CD8α- Invariant Natural Killer T Cells

et al. 2011

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“…In combination, these subsets thus build up an acute defense system whose mobilization on epinephrine release allows for efficient surveillance of tissues and rapid accumulation at sites of injury and infection (22, 25-28, 42, 45, 48, 52-54). In this context, it would be of interest to examine the effect of epinephrine also on other cytotoxic effector leukocytes, for example, CD8 + type 1 NKT cells showing strong antitumor cytotoxicity (54,55).…”

Section: Discussionmentioning

confidence: 99%

Selective Mobilization of Cytotoxic Leukocytes by Epinephrine

Dimitrov

Lange

Born³

2009

The Journal of Immunology

193

150

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It is well-known that acute stress, presumably as a first defense against pathogens, enhances PBMC counts by mobilizing these β2-adrenoceptor positive cells from the marginal pool. Yet, only select leukocyte subsets participate in this phenomenon of adrenergic leukocytosis and underlying mechanisms are obscure. In this study, we analyzed in human blood adhesion molecule and chemokine receptor profiles in 14 leukocyte subsets, and responsiveness of subsets to epinephrine in vivo and in vitro. Five subsets, namely, CCR7−CD45RA+CD8+ effector T cells, CD4−CD8− γ/δ T cells, CD3+CD56+ NKT-like cells, CD16+CD56dim cytotoxic NK cells, and CD14dimCD16+ proinflammatory monocytes showed a rapid and transient increase after infusion of epinephrine at physiological concentrations. These cells were characterized by a CD62L−CD11abrightCX3CRbright phenotype, whereby expression of both CD11a and CX3CR1 was strongly correlated with adrenergic leukocytosis in vivo (r = 0.86 and 0.78, p < 0.005). The same subsets showed highest adherence to activated endothelium in vitro, which (except for proinflammatory monocytes) was reversed by epinephrine. We conclude that these five cytotoxic effector leukocyte subsets comprise the marginal pool by a CD11a/CX3CR1-mediated attachment to the endothelium. Epinephrine rapidly attenuates this attachment to allow demargination and release of the cells into the circulation that, because of their cytotoxic effector function, provide immediate protection from invading pathogens.

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“…i NKT cells are further classified into CD4 + and CD4 − CD8 − double negative (DN) populations in mice [3] whereas human NKT cells are CD4 + , CD8 + or DN [4]. It is thought that CD4 + type I NKT cells produce both Th1 and Th2 cytokines such as IFN-γ and IL-4, respectively, whereas DN type I NKT cells primarily produce Th1-type cytokines [5–7]. Moreover, studies have shown that type I NKT cells exert potent anti-tumor effects, whereas type II NKT cells suppress antitumor immune responses through their production of Th2 cytokines, namely IL-4 and IL-13 [8].…”

Section: Natural Killer T Cellsmentioning

confidence: 99%

Natural Killer T Cell Based Immunotherapy

Subrahmanyam

Sun²,

East³

et al. 2012

J Vaccines Vaccin

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Natural killer T (NKT) cells play an important immunoregulatory role and are thought to bridge the innate and adaptive immune responses. Following activation through cognate interactions with lipid antigen presented in the context of CD1d molecules, NKT cells rapidly produce a plethora of cytokines and can also mediate cytotoxicity. Due to their potent effector functions, extensive research has been performed to increase our understanding on how to effectively modulate these cells. In fact, NKT cell agonists have been used as vaccine adjuvants to enhance antigen specific T and B cell responses to infections and malignancy. In this review, we will focus on recent advances in NKT cell-based vaccination strategies. Given the role that NKT cells play in autoimmune disease, infectious diseases, cancer, transplant immunology and dermatology, it is important to understand how to effectively guide their effector functions in order to develop novel immunotherapeutic strategies.

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Comparative gene expression analysis of NKT cell subpopulations

Cited by 32 publications

References 69 publications

Distinct and Overlapping Effector Functions of Expanded Human CD4+, CD8α+ and CD4-CD8α- Invariant Natural Killer T Cells

Distinct and Overlapping Effector Functions of Expanded Human CD4+, CD8α+ and CD4-CD8α- Invariant Natural Killer T Cells

Selective Mobilization of Cytotoxic Leukocytes by Epinephrine

Natural Killer T Cell Based Immunotherapy

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