Cellular Interactions in Lymph Node Development

Cupedo, Tom; Mebius, Reina E.

doi:10.4049/jimmunol.174.1.21

Cited by 113 publications

(88 citation statements)

References 66 publications

(77 reference statements)

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“…In contrast, control BALB-HIS mice only exhibited rare mesenteric lymph nodes (7,8). It is known that lymphoid tissue inducer cells are strongly reduced in IL-2Rγc −/− mice because of lack of IL-7 signaling (35). Adult Rag2 −/− IL-2Rγc −/− mice lack Peyer's patches and exhibit rudimental anlagen of peripheral lymph nodes (4)(5)(6).…”

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.

171

155

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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

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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.

171

155

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“…Based on the findings in this study and slightly modifying the models presented previously (10,47), we propose following four sequential stages of SLO organogenesis from anatomical and stromal viewpoints (Fig. 11).…”

Section: Discussionmentioning

confidence: 99%

Organizer-Like Reticular Stromal Cell Layer Common to Adult Secondary Lymphoid Organs

Katakai

Suto

Sugai

et al. 2008

The Journal of Immunology

216

282

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Mesenchymal stromal cells are crucial components of secondary lymphoid organs (SLOs). Organogenesis of SLOs involves specialized stromal cells, designated lymphoid tissue organizer (LTo) in the embryonic anlagen; in the adult, several distinct stromal lineages construct elaborate tissue architecture and regulate lymphocyte compartmentalization. The relationship between the LTo and adult stromal cells, however, remains unclear, as does the precise number of stromal cell types that constitute mature SLOs are unclear. From mouse lymph nodes, we established a VCAM-1+ICAM-1+MAdCAM-1+ reticular cell line that can produce CXCL13 upon LTβR stimulation and support primary B cell adhesion and migration in vitro. A similar stromal population sharing many characteristics with the LTo, designated marginal reticular cells (MRCs), was found in the outer follicular region immediately underneath the subcapsular sinus of lymph nodes. Moreover, MRCs were commonly observed at particular sites in various SLOs even in Rag2−/− mice, but were not found in ectopic lymphoid tissues, suggesting that MRCs are a developmentally determined element. These findings lead to a comprehensive view of the stromal composition and architecture of SLOs.

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“…ϩ IL-7R␣ ϩ lymphoid tissue inducer cells is compromised and formation of most lymph nodes is therefore impaired (53). Consequently, the search for a mouse strain lacking NK cells, but still harboring normal lymph node development is of interest.…”

Section: Cd4mentioning

confidence: 99%

Experimental Models to Study Development and Function of the Human Immune System In Vivo

Legrand

Weijer

Spits

2006

The Journal of Immunology

168

177

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The study of development and function of the immune system in vivo has made intensive use of animal models, but performing such work in humans is difficult for experimental, practical, and ethical reasons. Confronted with this scientific challenge, several pioneering groups have developed in the late 1980s mouse models of human immune system development. Although these experimental approaches were proven successful and useful, they were suffering from limitations due to xenograft transplantation barriers. By reviewing the characteristics of the successive models over the last 20 years, it becomes apparent that screening of potentially interesting mouse strains and usage of combinations of genetic deficiencies has led to major advances. This is particularly true for human T cell development in the murine thymus. This review will focus on these advances and the potential future improvements that remain to be accomplished.

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Cellular Interactions in Lymph Node Development

Cited by 113 publications

References 66 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

Organizer-Like Reticular Stromal Cell Layer Common to Adult Secondary Lymphoid Organs

Experimental Models to Study Development and Function of the Human Immune System In Vivo

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