Germ‐line and rearranged <i>Tcrd</i> transcription distinguish <i>bona fide</i> NK cells and NK‐like γδ T cells

Stewart, Charles A.; Walzer, Thierry; Robbins, Scott H.; Malissen, Bernard; Vivier, Éric; Prinz, Immo

doi:10.1002/eji.200737354

Cited by 73 publications

(80 citation statements)

References 55 publications

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“…Notably, NK1.1 1 and CCR6 1 expression identified the most effective IFN-g-and IL-17A-producing gd T cells, respectively. Our results are supported by our previous data, which proposed that NK1.1 1 gd T cells with very low levels of gd TCR on their cell surface (NK-like gd T cells [33]) have common characteristics and functional overlap with NK cells. Next, we compared the cytokine production of NK1.1 -and NK1.1 1 gd T cells in response to TCR-specific and unspecific stimulation.…”

Section: Different Stimulation Requirements For Il-17a or Ifn-c Produsupporting

confidence: 92%

CCR6 and NK1.1 distinguish between IL‐17A and IFN‐γ‐producing γδ effector T cells

et al. 2009

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cd T cells are a potent source of innate IL-17A and IFN-c, and they acquire the capacity to produce these cytokines within the thymus. However, the precise stages and required signals that guide this differentiation are unclear. Here we show that the CD24 low CD44 high effector cd T cells of the adult thymus are segregated into two lineages by the mutually exclusive expression of CCR6 and NK1.1. Only CCR6 1 cd T cells produced IL-17A, while NK1.1 1 cd T cells were efficient producers of IFN-c but not of IL-17A. Their effector phenotype correlated with loss of CCR9 expression, particularly among the NK1.1 1 cd T cells. Accordingly, both cd T-cell subsets were rare in gut-associated lymphoid tissues, but abundant in peripheral lymphoid tissues. There, they provided IL-17A and IFN-c in response to TCR-specific and TCR-independent stimuli. IL-12 and IL-18 induced IFN-c and IL-23 induced IL-17A production by NK1.1 1 or CCR6 1 cd T cells, respectively. Importantly, we show that CCR6 1 cd T cells are more responsive to TCR stimulation than their NK1.1 1 counterparts. In conclusion, our findings support the hypothesis that CCR6 1 IL-17A-producing cd T cells derive from less TCR-dependent selection events than IFN-c-producing NK1.1 1 cd T cells.Key words: gd T cells . CCR6 . IFN-g . IL-17A . Innate lymphocytes . NK1.1 Introduction IL-17A and IFN-g are generally regarded as pro-inflammatory effector cytokines that can be produced by Th cells but also by innate lymphocytes such as NK cells, NKT cells and gd T cells. While macrophage activation is supposed to be the main role of IFN-g, the induction of granulopoiesis is ascribed as a key biological function of IL-17A [1]. It is currently emerging that gd T cells are a potent source of IL-17A in the early phases of immune responses (reviewed in [2]). gd T cells constitute a large fraction of all IL-17A-producing cells in healthy mice and humans and are able to secrete IL-17A much more rapidly than CD4 1 Th17 cells [3][4][5]. These observations led to the concept that gd T cells are important players in a transitional response between innate and adaptive immune reactions [6]. The production of innate IL-17A by gd T cells appears to be essential in situations where an effective defence against extra-cellular bacteria or fungi relies on the fast mobilization of neutrophils [4,[6][7][8][9]. Moreover, IL-17A-producing gd T cells have been described to play important roles in immunopathologic diseases such as collageninduced arthritis [10], experimental pulmonary fibrosis [11], and in experimental autoimmune encephalitis [12,13].In contrast to CD4 1 Th cells that can develop into Th17 cells after encounter of specific cognate TCR Ag [14][15][16], it is not clear which stimuli induce IL-17A production by gd T cells in vivo. This essentially results from a lack of information about physiological gd TCR ligands. However, the current literature suggests that the decision whether a gd T cell will produce IL-17A is linked to 3488thymic development. Jensen et al. introduced a concept th...

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Section: Different Stimulation Requirements For Il-17a or Ifn-c Produsupporting

confidence: 92%

CCR6 and NK1.1 distinguish between IL‐17A and IFN‐γ‐producing γδ effector T cells

et al. 2009

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“…With respect to the CD3 subunits, Stewart et al [3] did not detect CD3e proteins in the cytoplasm of mouse NK cells. However, human NK cell clones established from fetal liver, which do not rearrange TCRb, TCRc, or TCRd genes, expressed CD3d, CD3c, and CD3e proteins in their cytoplasm, but not on their cell surface, and CD3e is transcribed by IL-2 activated human peripheral blood NK cells [7].…”

Section: Tcr Rearrangement and Expressionmentioning

confidence: 94%

“…Early studies from several laboratories established that mouse and human NK cells do not rearrange the TCR genes; however, germline transcription of TCRb and TCRd in NK cells has been reported previously [4][5][6]. The presence study in this issue of EJI by Stewart et al [3] provide an elegant demonstration of germline transcription of the TCRd locus in most resting, mature mouse NK cells in spleen, lymph nodes, and liver. Expression of germline transcripts of TCR and Ig loci have been documented in several cell types, and likely just represent accessibility of the gene region rather than having functional significance or developmental consequences.…”

Section: Tcr Rearrangement and Expressionmentioning

confidence: 99%

“…Similar difficulties have been encountered in studying the ab-TCR-bearing "NKT cells", which when activated down-regulate expression of their cell surface CD3/TCR complex -hence, making them almost impossible to distinguish from conventional NK cells. The observations reported by Stewart et al [3], underline the problem of discriminating between NK cells and T cells, and prompt reconsideration about what is known about CD3, TCR, and NK receptor expression in NK cells and T cells.…”

Section: Introductionmentioning

confidence: 99%

“…In this study, Stewart et al [3] analyzed the lymphocytes in mice expressing a green fluorescent protein (GFP) inserted into the T cell receptor (TCR)-d constant region gene. As expected, mature cd-TCR + T cells in these mice expressed high amounts of GFP and a CD3/TCR-cd complex was readily detected on the cell surface of these T cells.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Back to the future –defining NK cells and T cells

Lanier

2007

Eur J Immunol

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In this issue of the European Journal of Immunology (EJI), Stewart et al. report about a population of cd-T cells expressing an extensive repertoire of NK cell receptors, and the presence of non-rearranged germline TCRd transcripts in conventional NK cells. These findings and other recent studies highlight the similarities of NK cells and T cells and the problems in discriminating between these two lineages.

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The gene expression profile of phosphoantigen‐specific human γδ T lymphocytes is a blend of αβ T‐cell and NK‐cell signatures

et al. 2011

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Global transcriptional technologies have revolutionised the study of lymphoid cell populations, but human cd T lymphocytes specific for phosphoantigens remain far less deeply characterised by these methods despite the great therapeutic potential of these cells. Here we analyse the transcriptome of circulating TCRVc 1 cd T cells isolated from healthy individuals, and their relation with those from other lymphoid cell subsets. We report that the gene signature of phosphoantigen-specific TCRVc 1 cd T cells is a hybrid of those from ab T and NK cells, with more 'NK-cell' genes than ab T cells have and more 'T-cell' genes than NK cells. The expression profile of TCRVc 1 cd T cells stimulated with phosphoantigen recapitulates their immediate physiological functions: Th1 cytokine, chemokine and cytotoxic activities reflect their high mitotic activity at later time points and do not indicate antigen-presenting functions. Finally, such hallmarks make the transcriptome of cd T cells, whether resting or clonally expanding, clearly distinctive from that of NK/T or peripheral T-cell lymphomas of the cd subtype.

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Germ‐line and rearranged Tcrd transcription distinguish bona fide NK cells and NK‐like γδ T cells

Cited by 73 publications

References 55 publications

CCR6 and NK1.1 distinguish between IL‐17A and IFN‐γ‐producing γδ effector T cells

CCR6 and NK1.1 distinguish between IL‐17A and IFN‐γ‐producing γδ effector T cells

Back to the future –defining NK cells and T cells

The gene expression profile of phosphoantigen‐specific human γδ T lymphocytes is a blend of αβ T‐cell and NK‐cell signatures

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