scholarly journals Lack of Peripherally Induced Tolerance to Established Skin Allografts in Immunologically ReconstitutedScidMice

1992 ◽  
Vol 3 (1) ◽  
pp. 45-50 ◽  
Author(s):  
T. V. Rajan ◽  
Leonard D. Shultz ◽  
Dale L. Greinert
Keyword(s):  
Immune System ◽  
Fetal Liver ◽  
Present Report ◽  
Model System ◽  
Scid Mice ◽  
Peripheral Tolerance ◽  
Skin Grafts ◽  
Skin Allograft ◽  
Clonal Deletion ◽  
Skin Allografts

The mechanism by which the antigen-specific immune system distinguishes between foreign antigens (toward which it mounts an immune response) and self-antigens (of which it is tolerant) is not completely understood. Studies using “superantigens” and transgenic mice have allowed investigations into some of the mechanisms of clonal deletion, anergy, and peripheral tolerance. In the present report, we have attempted to develop a new model system to investigate the possible mechanism(s) of peripheral tolerance to allografts. In this system, skin grafts from C57BL/6J (B6;H-2bmice are grafted onto T- and B-lymphocyte-deficient C.B-17-scid/scid(H-2d; hereafter referred to asscid) mice. Because of their lack of functional lymphocytes, thescidmice readily accept the allogeneic skin grafts. After the allografts healed, the scid mice were reconstituted with T-cell-deficient fetal liver from coisogeneic C.B-17-∤/∤ mice or bone marrow from weanling congenitally athymic BALB/c-nu/nu(H-2d; hereafter referred to asnude) mice. Upon immunological reconstitution, the scid mice reiected the established B6 skin allografts, suggesting that an immune system developing in the presence of an intact peripheral skin allograft fails to develop tolerance to the peripheral allograft. This model system may be useful for the study of the mechanisms required for the induction of peripheral tolerance.

scholarly journals Mechanisms of the induction of autoimmunity

2005 ◽  
Vol 133 (Suppl. 1) ◽  
pp. 9-15 ◽  
Author(s):  
Marija Mostarica-Stojkovic
Keyword(s):  
Immune System ◽  
T Cell ◽  
Autoimmune Diseases ◽  
Molecular Mimicry ◽  
The Body ◽  
Peripheral Tolerance ◽  
High Avidity ◽  
Main Function ◽  
Clonal Deletion ◽  
Genetic Traits

The main function of the immune system is to protect the body by responding to invading microorganisms. Immunologic tolerance is the basic property of the immune system that provides for self/non-self discrimination so that the immune system can protect the host from external pathogens without reacting against itself. Central tolerance is achieved by the clonal deletion of self-reactive lymphocytes expressing receptors with high avidity for self. Autoreactive lymphocytes which escaped selection in the central lymphoid organs are present in the peripheral repertoire but but are kept under control by multiple diverse peripheral tolerance mechanisms acting either directly on the self-reactive T cell (T-cell intrinsic) or indirectly via additional cells (T-cell extrinsic). Intrinsic mec hanisms include ignorance of autoantigens, anergy, phenotype skewing or activation-induced cell death of autoreactive T lymphocytes, while extrinsic mechanisms act through immature and/ or tolerogenic dendritic cells as well as different types of regulatory cells. Autoimmune diseases are associated with humoral or cell-mediated immune reactions against one or more of the body?s own constituents. Activation and clonal expansion of autoreactive lymhocytes is a crucial step in the pathogenesis of autoimmune diseases. They result from the complex interactions between genetic traits and environmental factors, among which infections are the most likely cause. Several basic mechanisms may be operating whereby an infectious agent actually induces apparent autoimmne reactivity including molecular mimicry, bystander activation, induction of costimulation, polyclonal activation, altered processing and expression of cryptic antigens. Although many questions regarding autotolerance and etiop athogenestis of autoimmunity have yet to be resolved, it is evident that multiple overlapping pathways are operative in establishing, maintaining and breaking autotolerance, as well as during the initiation, progression, and final effector phases of autoimmunity.

Ex vivo–expanded DCs induce donor-specific central and peripheral tolerance and prolong the acceptance of donor skin grafts

Blood ◽  
2011 ◽  
Vol 117 (9) ◽  
pp. 2640-2648 ◽  
Author(s):  
Tomoyoshi Yamano ◽  
Sho Watanabe ◽  
Hiroyuki Hasegawa ◽  
Toshihiro Suzuki ◽  
Ryo Abe ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Ex Vivo ◽  
Peripheral Tolerance ◽  
Skin Grafts ◽  
Major Histocompatibility ◽  
Clonal Deletion ◽  
Activated T Cells ◽  
Donor Skin ◽  
Major Histocompatibility Complexes

Abstract Dendritic cells (DCs) are known to regulate immune responses by inducing both central and peripheral tolerance. DCs play a vital role in negative selection of developing thymocytes by deleting T cells with high-affinity for self-peptide–major histocompatibility complexes. In the periphery, DCs mediate peripheral tolerance by promoting regulatory T-cell development, induction of T-cell unresponsiveness, and deletion of activated T cells. We studied whether allogeneic DCs, obtained from bone marrow cultured with either Flt3L (FLDCs) or granulocyte-macrophage colony-stimulating factor (GMDCs), could induce allospecific central and peripheral tolerance after IV injection; B cells were used as a control. The results showed that only FLDCs reached the thymus after injection and that these cells induced both central and peripheral tolerance to donor major histocompatibility complexes. For central tolerance, injection of FLDCs induced antigen-specific clonal deletion of both CD8 and CD4 single-positive thymocytes. For peripheral tolerance, injection of FLDCs induced donor-specific T-cell unresponsiveness and prolonged survival of donor-derived skin grafts. Tolerance induction by adoptive transfer of FLDCs could be a useful approach for promoting graft acceptance after organ transplantation.

Induction de la tolérance aux allogreffes de peau dans les chimères de l'amphibien urodèle, Pleurodeles waltlii Michah

Development ◽  
1974 ◽  
Vol 32 (3) ◽  
pp. 805-818
Author(s):  
Par P. Goujon
Keyword(s):  
Adult Stage ◽  
Posterior Part ◽  
The Other ◽  
Skin Grafts ◽  
Skin Allograft ◽  
Reciprocal Exchange ◽  
Other Hand ◽  
Skin Allografts ◽  
Pleurodeles Waltlii ◽  
Natural Tolerance

Induction of skin allograft tolerance in chimaeras of urodele amphibian, Pleurodeles waltlii Michah. Allogenic chimaeras were produced in Pleurodeles waltlii (Amphibian, Urodele) by associating the anterior and the posterior parts of two different embryos. A reciprocal exchange between two homologue embryos gave rise to reciprocal allogenic chimaeras. Skin grafts performed in the adult stage between two reciprocal chimaeras are always tolerated. On the other hand, when two skin grafts coming from the anterior and the posterior part of one chimaera are grafted on a common host, one of them may be tolerated and the other rejected: each part of a chimaera keeps its own antigenicity. In allogenic chimaeras, the average natural tolerance for skin allografts is 30 % higher than in sibling controls.

scholarly journals Deceased donor skin allograft banking: Response and utilization

2010 ◽  
Vol 43 (S 01) ◽  
pp. S114-S120
Author(s):  
Madhuri A. Gore ◽  
Anuradha S. De
Keyword(s):  
Burn Injury ◽  
Deceased Donor ◽  
Indian Society ◽  
Skin Substitutes ◽  
Skin Allograft ◽  
Medical College ◽  
Skin Allografts ◽  
Donor Skin ◽  
Life Saving ◽  
Feasible Option

ABSTRACT Background: In the absence of xenograft and biosynthetic skin substitutes, deceased donor skin allografts is a feasible option for saving life of patient with extensive burn injury in our country. Aims: The first deceased donor skin allograft bank in India became functional at Lokmanya Tilak Municipal (LTM) medical college and hospital on 24th April 2000. The response of Indian society to this new concept of skin donation after death and the pattern of utilization of banked allografts from 2000 to 2010 has been presented in this study. Settings and Design: This allograft skin bank was established by the department of surgery. The departments of surgery and microbiology share the responsibility of smooth functioning of the bank. Materials and Methods: The response in terms of number of donations and the profile of donors was analyzed from records. Pattern and outcome of allograft utilization was studied from specially designed forms. Results: During these ten years, 262 deceased donor skin allograft donations were received. The response showed significant improvement after counselling was extended to the community. Majority of the donors were above 70 years of age and procurement was done at home for most. Skin allografts from 249 donors were used for 165 patients in ten years. The outcome was encouraging with seven deaths in 151 recipients with burn injuries. Conclusions: Our experience shows that the Indian society is ready to accept the concept of skin donation after death. Use of skin allografts is life saving for large burns. We need to prepare guidelines for the establishment of more skin banks in the country.

scholarly journals NF-κB RelA-deficient Lymphocytes: Normal Development of  T Cells and B Cells, Impaired Production of IgA and IgG1 and Reduced Proliferative Responses

1997 ◽  
Vol 185 (5) ◽  
pp. 953-962 ◽  
Author(s):  
Takahiro S. Doi ◽  
Toshitada Takahashi ◽  
Osamu Taguchi ◽  
Takachika Azuma ◽  
Yuichi Obata
Keyword(s):  
T Cells ◽  
B Cells ◽  
Fetal Liver ◽  
Critical Role ◽  
Calcium Ionophore ◽  
Scid Mice ◽  
T And B Cells ◽  
Liver Transplants ◽  
Liver Degeneration ◽  
And Function

To investigate the function of NF-κB RelA (p65), we generated mice deficient in this NF-κB family member by homologous recombination. Mice lacking RelA showed liver degeneration and died around embryonic day 14.5. To elucidate the role of RelA in lymphocyte development and function, we transplanted fetal liver cells of 13.5-day embryos from heterozygote matings into irradiated SCID mice. Within 4 weeks, both T and B cells had developed in the SCID mice receiving relA−/− fetal liver transplants, similar to the relA+/+ and +/− cases. T cells were found to mature to Thy-1+/TCRαβ+/CD3+/CD4+ or CD8+, while B cells had the ability to differentiate to IgM+/B220+ and to secrete immunoglobulins. However, the secretion of IgG1 and IgA was reduced in RelA-deficient B cells. Furthermore, both T and B cells lacking RelA showed marked reduction in proliferative responses to stimulation with Con A, anti-CD3, anti-CD3+anti-CD28, LPS, anti-IgM, and PMA+calcium ionophore. The results indicate that RelA plays a critical role in production of specific Ig isotypes and also in signal transduction pathways for lymphocyte proliferation.

scholarly journals Platelet Gene Therapy Promotes Targeted Peripheral Tolerance by Clonal Deletion and Induction of Antigen-Specific Regulatory T Cells

2018 ◽  
Vol 9 ◽  
Author(s):  
Xiaofeng Luo ◽  
Juan Chen ◽  
Jocelyn A. Schroeder ◽  
Kenneth P. Allen ◽  
Christina K. Baumgartner ◽  
...  
Keyword(s):  
Gene Therapy ◽  
T Cells ◽  
Regulatory T Cells ◽  
Peripheral Tolerance ◽  
Clonal Deletion

Skin grafts

2021 ◽  
pp. 35-38
Author(s):  
Siobhan O’Ceallaigh ◽  
Mamta Shah
Keyword(s):  
Immune System ◽  
Blood Supply ◽  
Skin Graft ◽  
Burn Injuries ◽  
Skin Grafts ◽  
Skin Defects ◽  
Extensive Burn

Skin grafts are an option for closing skin defects that cannot be closed primarily. A skin graft consists of epidermis and a portion of the underlying dermis that is detached from its blood supply and transferred to another location, usually on the same individual (an autograft). Skin grafts can also be used from cadaver donors (allografts) in extensive burn injuries, but as the recipient’s immune system will eventually reject this foreign tissue, this is only a temporary measure.

Unique Differentiation Programs of Human Fetal Liver Stem Cells Shown Both In Vitro and In Vivo in NOD/SCID Mice

Blood ◽  
1999 ◽  
Vol 94 (8) ◽  
pp. 2686-2695 ◽  
Author(s):  
Franck E. Nicolini ◽  
Tessa L. Holyoake ◽  
Johanne D. Cashman ◽  
Pat P.Y. Chu ◽  
Karen Lambie ◽  
...  
Keyword(s):  
Cord Blood ◽  
Fetal Liver ◽  
Scid Mice ◽  
Human Cord Blood ◽  
Human Fetal Liver ◽  
Human Erythropoietin ◽  
Erythroid Precursors ◽  
Lower Ratio

Comparative measurements of different types of hematopoietic progenitors present in human fetal liver, cord blood, and adult marrow showed a large (up to 250-fold), stage-specific, but lineage-unrestricted, amplification of the colony-forming cell (CFC) compartment in the fetal liver, with a higher ratio of all types of CFC to long-term culture-initiating cells (LTC-IC) and a lower ratio of total (mature) cells to CFC. Human fetal liver LTC-IC were also found to produce more CFC in LTC than cord blood or adult marrow LTC-IC, and more of the fetal liver LTC-IC–derived CFC were erythroid. Human fetal liver cells regenerated human multilineage hematopoiesis in NOD/SCID mice with the same kinetics as human cord blood and adult marrow cells, but sustained a high level of terminal erythropoiesis not seen in adult marrow-engrafted mice unless exogenous human erythropoietin (Epo) was injected. This may be due to a demonstrated 10-fold lower activity of murine versus human Epo on human cells, sufficient to distinguish between a differential Epo sensitivity of fetal and adult erythroid precursors. Examination of human LTC-IC, CFC, and erythroblasts generated either in NOD/SCID mice and/or in LTC showed the types of cells and hemoglobins produced also to reflect their ontological origin, regardless of the environment in which the erythroid precursors were generated. We suggest that ontogeny may affect the behavior of cells at many stages of hematopoietic cell differentiation through key changes in shared signaling pathways.

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