Kidney graft survival in rats without immunosuppressants after intrathymic glomerular transplantation

Rossini, M; Imberti, Ornella; Perico, Norberto

doi:10.1016/0140-6736(91)91368-5

Cited by 121 publications

(29 citation statements)

References 16 publications

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“…Tolerance induction occurs in the thymus when immature thymocytes are selected to move into the mature thymocyte pool via interactions with self-antigens (38,39). Intrathymic antigen injection led to unresponsiveness to the same antigen in several experimental models (40,41). In this study we examined T cell proliferation and antibody production in response to ␤-gal as a self-antigen.…”

Section: Discussionmentioning

confidence: 99%

An acetylcholine receptor alpha subunit promoter confers intrathymic expression in transgenic mice. Implications for tolerance of a transgenic self-antigen and for autoreactivity in myasthenia gravis.

Salmon

Bruand²,

Cardona³

et al. 1998

J. Clin. Invest.

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Myasthenia gravis (MG) is an autoimmune disease targeting the skeletal muscle acetylcholine receptor (AChR). Although the autoantigen is present in the thymus, it is not tolerated in MG patients. In addition, the nature of the cell bearing the autoantigen is controversial. To approach these questions, we used two lineages of transgenic mice in which the ␤ -galactosidase ( ␤ -gal) gene is under the control of a 842-bp (Tg1) or a 3300-bp promoter fragment (Tg2)

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Section: Discussionmentioning

confidence: 99%

An acetylcholine receptor alpha subunit promoter confers intrathymic expression in transgenic mice. Implications for tolerance of a transgenic self-antigen and for autoreactivity in myasthenia gravis.

Salmon

Bruand²,

Cardona³

et al. 1998

J. Clin. Invest.

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“…Clonal deletion, which occurs in the thymus upon recognition of self-or allogeneic peptides by maturing T cells, is essential to the process of self (2, 10) and acquired transplant tolerance (3,(5)(6)(7)(8). However, the nature of humoral mediator(s) involved in this process is still elusive.…”

Section: Discussionmentioning

confidence: 99%

“…Acquired tolerance in experimental autoimmunity (2) and transplantation (3,4) can be thymus dependent and, indeed, in the rat, intrathymic injection of allogeneic cells or allo-Ags induced unresponsiveness to subsequent pancreatic islet (5), cardiac (6), and renal allografts (7,8). Our group reported that thymic recognition of immunogenic class II MHC synthetic allopeptides induced a state of donor-specific tolerance to allograft and prolonged the survival of kidney allografts in highresponder Wistar-Furth (WF, 3 RT1 u ) to Lewis (RT1 l ) rat strain combinations (7,9).…”

mentioning

confidence: 99%

Thymic Dendritic Cells Express Inducible Nitric Oxide Synthase and Generate Nitric Oxide in Response to Self- and Alloantigens

Aiello

Noris

Piccinini

et al. 2000

The Journal of Immunology

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Thymocytes maturing in the thymus undergo clonal deletion/apoptosis when they encounter self- or allo-Ags presented by dendritic cells (DCs). How this occurs is a matter of debate, but NO may play a role given its ability of inducing apoptosis of these cells. APC (a mixed population of macrophages (Mφ) and DCs) from rat thymus expressed high levels of inducible NO synthase (iNOS) and produced large amounts of NO in basal conditions whereas iNOS expression and NO production were very low in thymocytes. Analysis by FACS and by double labeling of cytocentrifuged preparations showed that DCs and MΦ both express iNOS within APC. Analysis of a purified preparation of DCs confirmed that these cells express high levels of iNOS and produce large amounts of NO in basal conditions. The capacity of DCs to generate NO was enhanced by exposure to rat albumin, a self-protein, and required a fully expressed process of Ag internalization, processing, and presentation. Peptides derived from portions of class II MHC molecules up-regulate iNOS expression and NO production by DCs as well, both in self and allogeneic combinations, suggesting a role of NO in both self and acquired tolerance. We also found that NO induced apoptosis of rat double-positive thymocytes, the effect being more evident in anti-CD3-stimulated cells. Altogether, the present findings might suggest that DC-derived NO is at least one of the soluble factors regulating events, in the thymus, that follow recognition of self- and allo-Ags.

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“…Many years ago, Makinodan and colleagues 5 proposed that healthy T cells be collected in youth, frozen, and given back to the donor in old age to correct immunodeficiency. As immunologic tolerance induction becomes more successful, cryopreservation of young donor organs to allow time for donor-specific tolerance to be developed in the planned older recipient 6,7 could have a major impact on the present field of transplantation. The focus of the present paper is on the relevance of cryopreservation to the next few steps in regenerative medicine, in which increasingly complex new products of tissue engineering and stem cell biology are successfully applied to the correction of age-related deficits.…”

Section: Introduction Cmentioning

confidence: 99%

Cryopreservation of Complex Systems: The Missing Link in the Regenerative Medicine Supply Chain

Fahy

Wowk

2006

Rejuvenation Research

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Transplantation can be regarded as one form of "antiaging medicine" that is widely accepted as being effective in extending human life. The current number of organ transplants in the United States is on the order of 20,000 per year, but the need may be closer to 900,000 per year. Cadaveric and living-related donor sources are unlikely to be able to provide all of the transplants required, but the gap between supply and demand can be eliminated in principle by the field of regenerative medicine, including the present field of tissue engineering through which cell, tissue, and even organ replacements are being created in the laboratory. If so, it could allow over 30% of all deaths in the United States to be substantially postponed, raising the probability of living to the age of 80 by a factor of two and the odds of living to 90 by more than a factor of 10. This promise, however, depends on the ability to physically distribute the products of regenerative medicine to patients in need and to produce these products in a way that allows for adequate inventory control and quality assurance. For this purpose, the ability to cryogenically preserve (cryopreserve) cells, tissues, and even whole laboratory-produced organs may be indispensable. Until recently, the cryopreservation of organs has seemed a remote prospect to most observers, but developments over the past few years are rapidly changing the scientific basis for preserving even the most difficult and delicate organs for unlimited periods of time. Animal intestines and ovaries have been frozen, thawed, and shown to function after transplantation, but the preservation of vital organs will most likely require vitrification. With vitrification, all ice formation is prevented and the organ is preserved in the glassy state below the glass transition temperature (T G ). Vitrification has been successful for many tissues such as veins, arteries, cartilage, and heart valves, and success has even been claimed for whole ovaries. For vital organs, a significant recent milestone for vitrification has been the ability to routinely recover rabbit kidneys after cooling to a mean intrarenal temperature of about Ϫ45°C, as verified by life support function after transplantation. This temperature is not low enough for long-term banking, but research continues on preservation below Ϫ45°C, and some encouraging preliminary evidence has been obtained indicating that kidneys can support life after vitrification. Full development of tissue engineering and organ generation from stem cells, when combined with the ability to bank these laboratory-produced products, in theory could dramatically increase median life expectancy even in the absence of any improvements in mitigating aging processes on a fundamental level. 279

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Kidney graft survival in rats without immunosuppressants after intrathymic glomerular transplantation

Cited by 121 publications

References 16 publications

An acetylcholine receptor alpha subunit promoter confers intrathymic expression in transgenic mice. Implications for tolerance of a transgenic self-antigen and for autoreactivity in myasthenia gravis.

An acetylcholine receptor alpha subunit promoter confers intrathymic expression in transgenic mice. Implications for tolerance of a transgenic self-antigen and for autoreactivity in myasthenia gravis.

Thymic Dendritic Cells Express Inducible Nitric Oxide Synthase and Generate Nitric Oxide in Response to Self- and Alloantigens

Cryopreservation of Complex Systems: The Missing Link in the Regenerative Medicine Supply Chain

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