Requirement for membrane lymphotoxin in natural killer cell development

Iizuka, Kinji; Chaplin, David; Wang, Yang; Wu, Qiang; Pegg, Lyle E.; Yokoyama, Wayne M.; Fu, Yang–Xin

doi:10.1073/pnas.96.11.6336

Cited by 125 publications

(83 citation statements)

References 26 publications

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“…While this manuscript was in preparation, impaired function of NK cells in LT␣ Ϫ/Ϫ mice was reported (58,59,63), consistent with the possibility that NK and NK T cells share a common precursor. The precise details of the process by which LT affects NK cells remain controversial.…”

Section: Discussionsupporting

confidence: 62%

Membrane Lymphotoxin Is Required for the Development of Different Subpopulations of NK T Cells

Elewaut¹,

Brossay²,

Santee

et al. 2000

The Journal of Immunology

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The development of lymphoid organs requires membrane-bound lymphotoxin (LT), a heterotrimer containing LTα and LTβ, but the effects of LT on T cell function have not been characterized extensively. Upon TCR cross-linking in vitro, splenocytes from both LTα−/− and LTβ−/− mice failed to produce IL-4 and IL-10 due to a reduction in NK T cells. Concordantly, LTα−/− and LTβ−/− mice did not respond to the lipoglycan α-galactosylceramide, which is presented by mouse CD1 to Vα14+ NK T cells. Interestingly, both populations of NK T cells, including those that are mouse CD1 dependent and α-galactosylceramide reactive and those that are not, were affected by disruption of the LTα and LTβ genes. NK T cells were not affected, however, in transgenic mice in which LT signaling is blocked, beginning on day 3 after birth, by expression of a soluble decoy LTβ receptor. This suggests that membrane-bound LT is critical for NK T cells early in ontogeny, but not for the homeostasis of mature cells.

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Section: Discussionsupporting

confidence: 62%

Membrane Lymphotoxin Is Required for the Development of Different Subpopulations of NK T Cells

Elewaut¹,

Brossay²,

Santee

et al. 2000

The Journal of Immunology

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“…Thus, it appears that there are some factors released by stroma that could be important for the fi rst steps of induction towards NK cells lineage but acquisition of receptors seems to be independent of stroma signals. Some published data refers that NK cells receptors are acquired in an orderly and nonrandom manner during in vitro human NK cell differentiation (Miller & McCullar, 2001;Mrozek, Anderson, & Caligiuri, 1996;Grzywacz et al, 2006) and, differing from our results, indicated that the fi rst inhibitory receptor to be surface-expressed is CD94/NKG2A while KIRs appear only later and in low percentages (Briard, Brouty-Boye, Azzarone, & Jasmin, 2002;Iizuka et al, 1999;Grzywacz et al, 2006;Miller & McCullar, 2001). Cytotoxicity results were consistent with the phenotypic behavior implying that these NK cells can demonstrate specifi city in the recognition process.…”

Section: Differentiation Of Natural Killer Cells From Human Umbilicalcontrasting

confidence: 34%

Ex vivo differentiation of natural killer cells from human umbilical cord blood CD34⁺progenitor cells

Pinho

Punzel²,

Sousa

et al. 2011

Cell Communication & Adhesion

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Natural Killer (NK)-cells are peripheral blood lymphocytes that represent an important arm of the innate immune system. NK-cells play a critical role in the immune surveillance against tumors and virally infected cells in a major histocompatibiliy complex (MHC)-unrestricted fashion. We have explored such capacities of NK-cells after differentiation from hematopoietic stem and progenitor cells derived from human umbilical cord blood. Several culture conditions have been established supporting proliferation and subsequent differentiation of these cells in terms of receptor expression and specifi c lysis depending on the growth conditions in the presence and absence of supportive stromal feeders. We show that acquisition of Killer Immunoglobulin Receptor (KIR) as well as NK Cytotoxicity Receptor expressions is independent of culture condition whereas absence of stromal feeders did not support acquisition of CD94/NKG2A expression. Such KIR-positive/ NKG2A-negative cells generated under different culture conditions showed strong and specifi c cytolytic activity which could have impact on further immunotherapeutic strategies.

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“…In line with this, mice lacking LNs due to knockout of the helix-loop-helix inhibitor Id2 gene (Id2 Ϫ/Ϫ ) are deficient in NK cells but not T or B lymphocytes (7). Moreover, lymphotoxin ␣ (Lta)-deficient mice show impaired LN organogenesis and defective NK cell development (8). However, none of these observations provides incontrovertible evidence that LNs are significant sites of NK cell differentiation or development.…”

Section: T Regulatory Cells Control Numbers Of Nk Cells and Cd8␣mentioning

confidence: 80%

T Regulatory Cells Control Numbers of NK Cells and CD8α+ Immature Dendritic Cells in the Lymph Node Paracortex

Giroux

Yurchenko

St.-Pierre

et al. 2007

The Journal of Immunology

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The spleen contains numerous NK cells whose differentiation profile is characterized by a preponderance of mature elements located mainly in the red pulp. In contrast, lymph nodes (LNs) contain few NK cells and they are sited mostly in T cell zones and skewed toward immature developmental stages. We show that, in mice, naturally occurring CD4+Foxp3+ regulatory T (Treg) cells are both necessary and sufficient to repress accumulation of NK cells in resting LNs. Moreover, we present evidence that Treg cells hamper generation of mature NK cells through short-range interactions with NK precursors. In turn, mature NK cells specifically regulate the amount of CD8α+ phenotypically immature dendritic cells present in LN T cell zones. We propose that the dominant influence of Treg cells on NK cell precursors and CD8α+ immature dendritic cells explains why “quiescent” LNs in the absence of infection function as privileged sites for induction and maintenance of tolerance to peripheral Ags.

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Requirement for membrane lymphotoxin in natural killer cell development

Abstract: Development of natural killer (NK) cells is thought to depend on interactions between NK progenitors

Cited by 125 publications

References 26 publications

Membrane Lymphotoxin Is Required for the Development of Different Subpopulations of NK T Cells

Membrane Lymphotoxin Is Required for the Development of Different Subpopulations of NK T Cells

Ex vivo differentiation of natural killer cells from human umbilical cord blood CD34⁺progenitor cells

T Regulatory Cells Control Numbers of NK Cells and CD8α+ Immature Dendritic Cells in the Lymph Node Paracortex

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Requirement for membrane lymphotoxin in natural killer cell development

Abstract: Development of natural killer (NK) cells is thought to depend on interactions between NK progenitors

Cited by 125 publications

References 26 publications

Membrane Lymphotoxin Is Required for the Development of Different Subpopulations of NK T Cells

Membrane Lymphotoxin Is Required for the Development of Different Subpopulations of NK T Cells

Ex vivo differentiation of natural killer cells from human umbilical cord blood CD34+progenitor cells

T Regulatory Cells Control Numbers of NK Cells and CD8α+ Immature Dendritic Cells in the Lymph Node Paracortex

Contact Info

Product

Resources

About

Ex vivo differentiation of natural killer cells from human umbilical cord blood CD34⁺progenitor cells