Neonatal Tolerance Revisited: Turning on Newborn T Cells with Dendritic Cells

Ridge, J P; Fuchs, Ephraim J.; Matzinger, Polly

doi:10.1126/science.271.5256.1723

Cited by 731 publications

(472 citation statements)

References 52 publications

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“…We can attempt to convert tumour cells to antigenpresenting cells by making them more immunogenic (B7 co-stimulation); restore lost MHC molecules; transfect with cytokines capable of a direct stimulation of lymphocytes (IL-2) or even enhance tumour antigen release and its subsequent up-take by professional antigen-presenting cells (presuming that antigenspecific T cells are still in the circulation or can be generated from naive precursors). The last approach also conforms with a recently suggested 'Danger Model' (Ridge et al, 1996) theory according to which induced necrosis may attract antigen-presenting cells (macrophages, dendritic cells), increase their up-take and the subsequent delivery of antigen in an appropriate fashion to T lymphocytes. The recruitment of antigen-presenting cells can be further potentiated by the local production of GM-CSF or IL-12.…”

Section: Gene and Adoptive Immunotherapysupporting

confidence: 70%

Sticky and smelly issues: lessons on tumour cell and leucocyte trafficking, gene and immunotherapy of cancer

Alexandroff¹,

McIntyre

Porter

et al. 1998

Br J Cancer

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Summary The Second Meeting of the British Society for Immunology Tumour Immunology Affinity Group (TIAG) took place at King's College (London, UK) on 17-18 June 1997 and brought together over 100 tumour immunologists from the UK and abroad. In contrast to previous meetings the focus of the meeting was on the role of adhesion in immunosurveillance and tumour dissemination. In addition, recent achievements in the areas of chemokines, cytotoxic T-lymphocyte (CTL) and natural killer (NK) cells, co-stimulation, gene and adoptive immunotherapy were also addressed. The purpose of this report is to outline current trends in tumour immunology.Keywords: gene and adoptive cancer immunotherapy; cell adhesion; chemotaxis; apoptosis; natural killer cells ADHESION AND CHEMOTAXISThe conference began with an overview of cell adhesion molecules in the interaction of leucocyte and tumour cells with the endothelium (Dr N Hogg, London, UK). Well-known adhesive ligands were described including PSGL-1 (a ligand for all three selectins, especially relevant for neutrophil adhesion), CD44 [as a rolling receptor for haematopoietic (DeGrendele et al, 1996) and potentially non-haematopoietic cells, such as pancreatic carcinoma and melanoma] and a4p1 (adherence receptor for leucocytes and tumour cells) ( Figure 1). The role of cell adhesion in leucocyte activation ('in/out' signalling) was also highlighted. Furthermore, chemokines, with few exceptions (Szabo et al, 1997), appear unable to activate adhesion molecules (such as LFA-1) on nonprimed T lymphocytes, as 'naive' T cells do not express corresponding chemokine receptors. However, the adhesion molecules on activated leucocytes can be 'switched on' if chemokine receptors are cross-linked (e.g. the cross-linking of IL-8 receptors by IL-8 bound to extracellular matrix proteins). N Hogg also discussed the ability of the a4,Bl integrin complex to either facilitate (Matsuura et al, 1996) or inhibit (Qian et al, 1994) the metastasis of neoplastic cells by decreasing the invasive potential of melanoma and even by inducing apoptosis of lymphoma cells (if expressed in situ). Furthermore, additional studies described the ability of the metalloproteinase MMP2 to form a complex with aVP3 integrin (vitronectin R) (Brooks et al, 1996) and facilitate melanoma cell migration through its ability to digest collagen, unveiling its hidden RGD sequence and thus permitting integrin-mediated adhesion. In another model, the urokinase-type plasminogen activator receptor (uPAR) forms a complex with active integrins, which has the effect of destabilizing integrin adhesion and promoting adhesion and migration on vitronectin, thus potentially enhancing the invasive properties of tumour cells (Wei et al, 1996).The adhesion and trafficking mechanisms of lymphocyte transmigration in both normal and adjacent tumour endothelium remain poorly understood. In an elegant in vivo model using a mouse cremaster muscle implanted with a tumour and fluorescent confocal microscopy, murine lymphocytes were examined for their ability...

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Section: Gene and Adoptive Immunotherapysupporting

confidence: 70%

Sticky and smelly issues: lessons on tumour cell and leucocyte trafficking, gene and immunotherapy of cancer

Alexandroff¹,

McIntyre

Porter

et al. 1998

Br J Cancer

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“…20 Its establishment appears to be confined to a special phase during fetal and early development, when the immune system is prone to tolerate antigens rather than making classical immune responses. 20 Many hypotheses have been raised to explain it, 20,21 including that neonatal tolerance results from a T-cell inability to produce IL-2, 22,23 from the high numbers of non-functional immature T cells and low numbers of mature effector T cells, 20 from lack of professional antigen-presenting cells, 24,25 and from the high activity of suppressor cells. 26 More recently, it has been proposed that T-cell migration patterns in a neonatal environment might be of importance in establishing tissue-specific tolerance at birth.…”

Section: Discussionmentioning

confidence: 99%

Natural killer T cells are required for the development of a superantigen‐driven T helper type 2 immune response in mice

et al. 2005

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SummaryWe show, here, that one single injection or weekly injections of staphylococcal enterotoxin B (SEB), starting in 1-day-old newborn mice, induced a powerful immune response with a T helper type 2 (Th2) pattern, as judged by the isotype and cytokine profile, with the production of large amounts of SEB-specific immunoglobulin G1 (IgG1), detectable levels of SEB-specific IgE and increased production of interleukin-4 by spleen cells. These protocols also induced an increase in the levels of total IgE in the serum. Memory of SEB was transferred to secondary recipients by using total spleen cells from primed animals. The secondary humoral response in transferred mice was diminished if spleen cells from SEB-treated mice were previously depleted of CD3 + or Vb8 + T cells or NK1.1 + cells. In vivo depletion of NK1.1 + cells in adult mice resulted in a marked reduction in the SEB-specific antibody response in both the primary and secondary immune responses. Additionally, purified NK1.1 + T cells were able to perform SEB-specific helper B-cell actions in vitro and in vivo. These results suggest that NK1.1 + T cells are required for the full development of humoral immunological memory, whilst making neonatal tolerance to SEB unachievable.

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“…[32][33][34] However, it has been demonstrated that, under optimal costimulatory conditions or with allogenic dendritic cells, neonatal and adult T-cell responses are similar, showing the immunocompetence of the T cells. 34,35 The increased susceptibility of neonates to infections in general has been ascribed to the immaturity of their immune system, and, more specifically, to the particular conditions of antigen presentation and T-cell priming. 36,37 In agreement with these results, we found that APCs isolated from the spleens and mesenteric lymph nodes of aa-fed adult C57BL/6 mice expressed CD40, CD80 and CD86 at levels similar to those of APCs from suckling mice.…”

Section: Discussionmentioning

confidence: 99%

Antigenic dietary protein guides maturation of the host immune system promoting resistance to Leishmania major infection in C57BL/6 mice

Amaral¹,

Gomes-Santos²,

Paula-Silva³

et al. 2010

Immunology

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Summary The immature immune system requires constant stimulation by foreign antigens during the early stages of life to develop properly and to create efficient immune responses against later infections. We have previously shown that intake of antigenic dietary protein is critical for inducing maturation of the immune system as well as for the development of T helper type 1 (Th1) immunity. In this study, we show that administration of an amino acid (aa)‐based diet during the development of the immune system subsequently resulted in inefficient control of Leishmania major infection in adult C57BL/6 mice. Compared with mice fed a control protein‐containing diet, adult aa‐fed mice showed a decreased interferon (IFN)‐γ response to parasite antigens and insufficient production of nitric oxide (NO), which is crucial to parasite death. However, no deviation towards Th2‐specific immunity to L. major was observed. Phenotypic analysis of antigen‐presenting cells (APCs) from aa‐fed mice revealed deficient levels of the costimulatory molecules CD40 and CD80, and low levels of interleukin (IL)‐12 produced by peritoneal macrophages, revealing an early stage of maturation of these cells. APCs isolated from aa‐fed mice were unable to stimulate a Th1 response in vitro. Both phenotypic features of T cells from aa‐fed mice and their ability to produce a Th1 response in the presence of mature APCs were unaffected when compared with T cells from control mice. The results presented here support the notion that regulation of Th1 immunity to infection includes environmental factors such as dietary proteins, which provide a natural source of stimulation that contributes to the process of maturation of APCs.

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Neonatal Tolerance Revisited: Turning on Newborn T Cells with Dendritic Cells

Cited by 731 publications

References 52 publications

Sticky and smelly issues: lessons on tumour cell and leucocyte trafficking, gene and immunotherapy of cancer

Sticky and smelly issues: lessons on tumour cell and leucocyte trafficking, gene and immunotherapy of cancer

Natural killer T cells are required for the development of a superantigen‐driven T helper type 2 immune response in mice

Antigenic dietary protein guides maturation of the host immune system promoting resistance to Leishmania major infection in C57BL/6 mice

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