IL-15 availability conditions homeostasis of peripheral natural killer T cells

Ranson, Thomas; Vosshenrich, Christian A. J.; Corcuff, Erwan; Richard, Odile; Laloux, Véronique; Lehuen, Agnès; Santo, James P. Di

doi:10.1073/pnas.0535482100

Cited by 133 publications

(129 citation statements)

References 42 publications

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“…As mentioned above memory CD8 T cells [5,24], which are prominently present also in BM [41], TCRab NKT cells [25] and TCRcd cells [26] all depend on IL-15 for their peripheral survival. Indeed, it has been shown that NK cells compete with NKT cells [25] or with TCRcd cells [26] for the available IL-15. It is thus conceivable that the accelerated NK cell production in the absence of T cells is due to an increased availability of IL-15.…”

Section: Nk Cells In T Cell-deficient Micementioning

confidence: 78%

“…Similar to NK cells, memory CD8 T cells [5,24], TCRab NKT cells [25] and TCRcd cells [26] depend on IL-15 for their peripheral maintenance. However, while TCRcd and NK cells were reduced, the proportion of CD8 + memory T cells (of naive CD8 + T cells) is normal in B cell-deficient mice.…”

Section: Nk Cells In B Cell-deficient Micementioning

confidence: 99%

“…This is not unique to NK cells as the survival of memory CD8 T cells [5,24], TCRab NKT cells [25] and TCRcd cells [26] is also controlled by IL-15. Besides IL-15, little is known regarding factors, which control the size of the NK cell compartment.…”

Section: Introductionmentioning

confidence: 99%

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T and B lymphocytes exert distinct effects on the homeostasis of NK cells

2006

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There is growing evidence that lymphocytes impact the development and/or function of other lymphocyte populations. Based on such observations we have tested whether the NK cell compartment was phenotypically and functionally altered in the absence of B and/or T cells. Here we show that T cell deficiency significantly accelerates BM NK cell production and the subsequent seeding of splenic and liver NK cell compartments. In contrast, B cell deficiency reduces splenic NK cell survival. In the absence of T and B cells, the size of the NK cell compartments is determined by the combination of these positive and negative effects. Even though NK cell homeostasis is significantly altered, NK cells from T and/or B cell-deficient mice show a normal capacity to kill a susceptible target cell line and to produce IFN. Nevertheless, we noted that the usage of MHC class Ispecific Ly49 family receptors was significantly altered in the absence of T and/or B cells. In general, B cell deficiency expanded Ly49 receptor usage, while T cell deficiency exerted both positive and negative effects. These findings show that B and T cells significantly and differentially influence the homeostasis and the phenotype of NK cells.

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Section: Nk Cells In T Cell-deficient Micementioning

confidence: 78%

Section: Nk Cells In B Cell-deficient Micementioning

confidence: 99%

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T and B lymphocytes exert distinct effects on the homeostasis of NK cells

2006

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“…This expansion is driven by IL-7 and IL-15 of which the latter also regulates the homeostasis of NK cells [47,48]. CD8 1 memory effector T cells are known to restrict IL-15-dependent homeostasis of gd-T cells [49,50]. Furthermore, NK cells and CD8 1 T cells compete for IL-15 in lymphopenic mice [51].…”

mentioning

confidence: 99%

CD56^bright NK cells after hematopoietic stem cell transplantation are activated mature NK cells that expand in patients with low numbers of T cells

et al. 2010

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We studied early NK-cell recovery in 29 allografted patients undergoing different lymphoreductive regimens. Already at 2 wk after graft take, the number of NK cells had reached (supra)normal levels but NK-cell subsets were skewed. The number of CD56 dim CD16 bright NK cells was low and correlated strongly with the level of hematopoiesis, whereas the number of the more abundant NK cells expressing high levels of CD56 did not. Post-transplant CD56 bright NK cells (ptCD56 bright ) differed from CD56 bright NK cells in normal controls (CD56 bright ) in being HLA-DR-and perforin-positive, CCR7 À , CD27 À , CD127 À and mostly c-kit À . CD56 bright from normal controls stimulated by IL-15 in vitro (NK ) acquired all the characteristics distinguishing CD56 bright from ptCD56 bright . IL-2 exerted similar effects. Moreover, when cultured without cytokines, ptCD56 bright , CD56 bright and NK responded similarly by upregulating CD127 and c-kit but not CCR7. IL-12 stimulated IFN-c production in ptCD56 bright , whereas CD56 bright responded only to IL-12 plus IL-15. Hence, ptCD56 bright have all the features of cytokine-stimulated CD56 bright . Because only patients with low numbers of T cells had high numbers of ptCD56 bright , we conclude that ptCD56 bright are activated CD56 bright that expand while competing with T cells for the elevated post-transplant level of IL-15.Key words: HSC transplantation . Human . Natural killer cells IntroductionIn humans, most lymphocytes without rearranged antigenreceptors express CD56 and are referred to as NK cells. Accordingly, they can be identified on the basis of a CD3 À CD56 1 phenotype [1][2][3], which excludes the subpopulation of T cells that coexpress CD56. However, this long-established definition of NK cells may be inadequate because CD3 À CD56 1 lymphocytes are heterogeneous and capable of exerting various effector functions other than killing cells with altered expression of self-MHC. Furthermore, many CD3 À CD56 1 lymphocytes do not lyse NK-cell targets when tested ex vivo and only acquire lytic activity after in vitro stimulation with cytokines. In fact, the large granular CD3 À CD56 1 lymphocytes with ''natural'' cytotoxicity that express low levels of CD56 (CD56 dim ) and high levels of the Fcg-receptor type III (CD16) [1][2][3][4] represent only a minority of all of the CD3 À CD56 1 lymphocytes in the body [5,6]. CD56 dim that provide first-line defense against viruses [7,8] 3246less abundant population of NK cells in peripheral blood expresses much higher levels of CD56 (CD56 bright ), the receptor for IL-7 (CD127), the receptor for SCF c-kit, the lymph nodehoming receptor CCR7, and displays only little cytolytic activity [3][4][5][9][10][11][12]. Approximately, half of the CD56 bright in peripheral blood express CD27, a marker virtually absent from CD56 dim [13][14][15]. Hence, CD56 bright in peripheral blood are identical or closely related to the NK cells residing in secondary lymphoid organs (SLO) that produce cytokines to guide the adaptive immune response [4-6,...

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“…32 Both IL-2 and IL-15 cytokines are important in the development and maturation of NK cells. 49 Also, expression of CD122 by early progenitors uniquely marks the committed NKPs. 33 Both the initiation of CD122 expression and its level in p85a À/À NK cells were not affected, indicating that p85a is dispensable for this developmental step.…”

Section: Discussionmentioning

confidence: 99%

Deletion of PI3K-p85α gene impairs lineage commitment, terminal maturation, cytokine generation and cytotoxicity of NK cells

et al. 2008

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Class IA phosphotidylinositol-3-kinases (PI3Ks) are a family of p85/p110 heterodimeric lipid kinases that are important in regulating signaling events in B and T cells. However, their role in natural killer (NK) cells is not understood. Here, using mice that lack the regulatory p85a subunit and its alternatively spliced variants p55a/p50a (collectively termed as p85a À/À ), we defined the role of PI3K in NK cell development and function. p85a À/À mice had impaired lineage commitment leading to reduced NK cellularity in the bone marrow and liver. p85a À/À NK cells showed a defective Ly49 subset specification and a decreased expression of CD43. Lack of p85a severely reduced the NK-mediated cytotoxicity against tumor cells representing 'induced-self' and 'missing-self'. More importantly, NKG2D and NK1.1 receptor-mediated cytokine and chemokine generation was significantly compromised in p85a À/À NK cells. These results reveal a previously unrecognized role of p85a in the development, terminal maturation, cytokine/chemokine generation and tumor clearance of NK cells.

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IL-15 availability conditions homeostasis of peripheral natural killer T cells

Cited by 133 publications

References 42 publications

T and B lymphocytes exert distinct effects on the homeostasis of NK cells

T and B lymphocytes exert distinct effects on the homeostasis of NK cells

CD56^bright NK cells after hematopoietic stem cell transplantation are activated mature NK cells that expand in patients with low numbers of T cells

Deletion of PI3K-p85α gene impairs lineage commitment, terminal maturation, cytokine generation and cytotoxicity of NK cells

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IL-15 availability conditions homeostasis of peripheral natural killer T cells

Cited by 133 publications

References 42 publications

T and B lymphocytes exert distinct effects on the homeostasis of NK cells

T and B lymphocytes exert distinct effects on the homeostasis of NK cells

CD56bright NK cells after hematopoietic stem cell transplantation are activated mature NK cells that expand in patients with low numbers of T cells

Deletion of PI3K-p85α gene impairs lineage commitment, terminal maturation, cytokine generation and cytotoxicity of NK cells

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CD56^bright NK cells after hematopoietic stem cell transplantation are activated mature NK cells that expand in patients with low numbers of T cells