Role of T and NK cells and IL7/IL7r interactions during neonatal maturation of lymph nodes

Coles, Mark; Veiga-Fernandes, Henrique; Foster, Katie; Norton, Trisha; Pagakis, Stamatis N.; Seddon, Ben; Kioussis, Dimitris

doi:10.1073/pnas.0604183103

Cited by 55 publications

(50 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Adult Rag2 −/− IL-2Rγc −/− mice lack Peyer's patches and exhibit rudimental anlagen of peripheral lymph nodes (4)(5)(6). Still, these anlagen are normally generated during embryonic life and can be maintain during neonatal life in an IL-7/IL-7R-dependent fashion by colonizing hematopoietic cells (e.g., through the adoptive transfer of T or NK cells but not B cells within 1 wk of birth) (36). In HIS mice, proper CD47/SIRPα interactions may allow for the rapid development of human cells, supporting maturation of Rag2 −/− IL-2Rγc −/− mouse lymph node anlages.…”

Section: Discussionmentioning

confidence: 99%

Functional CD47/signal regulatory protein alpha (SIRPα) interaction is required for optimal human T- and natural killer- (NK) cell homeostasis in vivo

Legrand

Huntington

Nagasawa

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

169

155

View full text Add to dashboard Cite

The homeostatic control mechanisms regulating human leukocyte numbers are poorly understood. Here, we assessed the role of phagocytes in this process using human immune system (HIS) BALB/c Rag2 −/− IL-2Rγc −/− mice in which human leukocytes are generated from transplanted hematopoietic progenitor cells. Interactions between signal regulatory protein alpha (SIRPα; expressed on phagocytes) and CD47 (expressed on hematopoietic cells) negatively regulate phagocyte activity of macrophages and other phagocytic cells. We previously showed that B cells develop and survive robustly in HIS mice, whereas T and natural killer (NK) cells survive poorly. Because human CD47 does not interact with BALB/c mouse SIRPα, we introduced functional CD47/SIRPα interactions in HIS mice by transducing mouse CD47 into human progenitor cells. Here, we show that this procedure resulted in a dramatic and selective improvement of progenitor cell engraftment and human T-and NK-cell homeostasis in HIS mouse peripheral lymphoid organs. The amount of engrafted human B cells also increased but much less than that of T and NK cells, and total plasma IgM and IgG concentrations increased 68-and 35-fold, respectively. Whereas T cells exhibit an activated/memory phenotype in the absence of functional CD47/SIRPα interactions, human T cells accumulated as CD4 + or CD8 + single-positive, naive, resting T cells in the presence of functional CD47/SIRPα interactions. Thus, in addition to signals mediated by T cell receptor (TCR)/MHC and/or IL/IL receptor interactions, sensing of cell surface CD47 expression by phagocyte SIRPα is a critical determinant of T-and NK-cell homeostasis under steady-state conditions in vivo.hematopoiesis | humanized mice | leukocyte homeostasis

show abstract

Section: Discussionmentioning

confidence: 99%

Functional CD47/signal regulatory protein alpha (SIRPα) interaction is required for optimal human T- and natural killer- (NK) cell homeostasis in vivo

Legrand

Huntington

Nagasawa

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

169

155

View full text Add to dashboard Cite

show abstract

“…Although the reasons underlying the strong reduction in numbers of several LNs observed in adult IL-7 2/2 and g c 2/2 mice remain poorly defined, IL-7 availability also regulates the size of the pool of LTi cells in vivo (16), indicating that LN organogenesis may be defective in IL-7 2/2 and g c 2/2 mice due to low LTi cell numbers. Alternatively, LN organogenesis may occur normally, and lymphopenia prevents the maintenance of the LN anlage after birth (23).…”

Section: The Journal Of Immunologymentioning

confidence: 99%

The IL-7 Signaling Pathway Regulates Lymph Node Development Independent of Peripheral Lymphocytes

Chappaz

Finke

2010

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…In the absence of LT␣, iLN organogenesis grinds to a halt around E15 to E17. 51 Interestingly, lack of LT␣ 1 ␤ 2 binding to LT␤R does not appear to have an effect on the presence of V ϩ and I ϩ single-positive stromal cells, suggesting that either expression of these cell adhesion molecules is LT␣ 1 ␤ 2 independent, or that there is a functional redundancy between LT␣ 1 ␤ 2 and LIGHT (lymphotoxin-like inducible protein that competes with glycoprotein D for herpes virus entry on T cells) or other unknown LT␤R ligands and in the absence of the former, binding of LIGHT/other ligands to LT␤R is sufficient to induce expression of these molecules as shown in mesenteric LN development in Ltb Ϫ/Ϫ mice. 52 Indeed, fetal LTic's express Light mRNA.…”

Section: Inducer Cell Function During Ln Developmentmentioning

confidence: 99%

Lymphotoxin a-dependent and -independent signals regulate stromal organizer cell homeostasis during lymph node organogenesis

White

Carragher

Parnell

et al. 2007

Blood

View full text Add to dashboard Cite

Lymph nodes provide specialized stromal microenvironments that support the recruitment and organization of T cells and B cells, enabling them to effectively participate in immune responses. While CD4 ؉ 3 ؊ lymphoid tissue inducer cells (LTic's) are known to play a key role in influencing lymph node (LN) development, the mechanisms that regulate the development of stromal organizer cells are unclear. Here, we define an ontogenetic program of lymph node stromal cell maturation in relation to the requirement for LTic's. We also describe a lymph node reaggregation assay to study cell-cell interactions and lymphocyte recruitment to these organs that reproduces the in vivo events during lymph node development. In addition, analysis of the lymph node anlagen in normal and lymphotoxin a (LTa)-deficient embryos shows that LTamediated signaling is required to sustain proliferation and survival of stromal cells in vivo. Our data identify LTa-independent and LTa-dependent stages of lymph node development, and provide direct evidence for the role of LTic's during LN organogenesis.( IntroductionOne of the main features of the immune system is the cross-talk interaction between different cell types that ensures full activation of immune responses. The exchange of information between cells of the immune system occurs within specific microenvironments in secondary lymphoid organs such as the spleen, lymph nodes (LNs), and Peyer patches (PPs). Disruption or abnormal development of these microenvironments leads to ineffective adaptive immune responses, resulting in repetitive infections and decrease survival of the host.LN organogenesis during embryo development depends on successful interactions between bone marrow-derived lymphoid tissue inducer cells (LTic's) and mesenchymal organizer stromal cells. [1][2][3] The signals involved in these interactions are transmitted through ligands and receptors of the tumor necrosis factor family that converge in activation of the NF-B transcription factors, resulting in marked changes in gene expression. 4,5 Genetic approaches had shown the crucial roles of lymphotoxin ␤ receptor (Lt␤R) and receptor activator of NF-B (RANK) and their ligands in the development of LNs. For instance, Lta Ϫ/Ϫ mice and Ltbr Ϫ/Ϫ mice lack all LNs, Ltb Ϫ/Ϫ mice form only mesenteric LNs, and Rank Ϫ/Ϫ and Rank-l Ϫ/Ϫ mice develop only rudimentary mesenteric LNs. 3,[6][7][8][9][10] Similarly, mice deficient in the NF-B family proteins RelA and RelB lack all LNs, while Nfkb2 Ϫ/Ϫ and Ikka aa knock-in mice present with defects in peripheral LNs. [11][12][13][14][15][16] While LTic's express the membrane-bound LT␣ 1 ␤ 2 ligand, stromal cells express the LT␤R receptor. Engagement of LT␤R receptor on stromal cells results in production of chemokines such as CXCL13, CCL21, and CCL19, and cell adhesion molecules that will attract further LTic's that express the chemokine receptors CXCR5 and CCR7. [17][18][19] Subsequent formation of cell clusters between LTic's and organizer cells results in organization of specific areas in...

show abstract

Role of T and NK cells and IL7/IL7r interactions during neonatal maturation of lymph nodes

Abstract: imaging ͉ lymphoid organogenesis ͉ transgenic mice

Cited by 55 publications

References 44 publications

Functional CD47/signal regulatory protein alpha (SIRPα) interaction is required for optimal human T- and natural killer- (NK) cell homeostasis in vivo

Functional CD47/signal regulatory protein alpha (SIRPα) interaction is required for optimal human T- and natural killer- (NK) cell homeostasis in vivo

The IL-7 Signaling Pathway Regulates Lymph Node Development Independent of Peripheral Lymphocytes

Lymphotoxin a-dependent and -independent signals regulate stromal organizer cell homeostasis during lymph node organogenesis

Contact Info

Product

Resources

About