Cellular Basis of Skin Allograft Rejection: An In Vivo Model of Immune-Mediated Tissue Destruction

1992 ◽  
Vol 10 (1) ◽  
pp. 333-360 ◽  
Author(s):  
A S Rosenberg ◽  
A Singer
Keyword(s):  
Allograft Rejection ◽  
In Vivo Model ◽  
Tissue Destruction ◽  
Skin Allograft ◽  
Cellular Basis ◽  
Immune Mediated

scholarly journals Quantitative assessment of mouse skin transplant rejection using digital photography

2005 ◽  
Vol 39 (2) ◽  
pp. 209-214 ◽  
Author(s):  
F Schwoebel ◽  
J Barsig ◽  
A Wendel ◽  
J Hamacher
Keyword(s):  
Allograft Rejection ◽  
Transplant Rejection ◽  
Immunosuppressive Treatment ◽  
Mouse Skin ◽  
Digital Photography ◽  
In Vivo Model ◽  
Skin Allograft ◽  
Monitoring Method ◽  
Early Stages

Mouse skin transplantation is an established in vivo model used to investigate the T-cell-mediated immune response of acute allograft rejection. The critical endpoint of this model is complete rejection of the allograft. However, visual judgement of this end stage of rejection is an arbitrary process and difficult to standardize. To overcome this problem, we established a monitoring method based on digital photography. Serial pictures from skin allografts of individual animals (C57BL/6 on BALB/c) were taken with a digital camera mounted on a microsurgical microscope. Thereby, the description and the correct assessment of early stages of rejection were possible due to the magnification of grafts by the microscope. Rejection scores were introduced to describe different stages from retained to completely rejected grafts. With cyclosporine A as a standard immunosuppressive treatment, we showed that early stages of skin rejection were unambiguously identified. This procedure allows the earlier termination of the experiment and reduction of animal distress, and it can be re-evaluated anywhere and any time after completion. This study demonstrates the suitability of monitoring experimental skin allograft rejection by digital photography, entailing several refinements in animal experimentation, both for the researcher and for the animal.

Primary inflammation in human cystic fibrosis small airways

2002 ◽  
Vol 283 (2) ◽  
pp. L445-L451 ◽  
Author(s):  
Rabindra Tirouvanziam ◽  
Ibrahim Khazaal ◽  
Bruno Péault
Keyword(s):  
Cystic Fibrosis ◽  
Severe Combined Immunodeficiency ◽  
In Vivo Model ◽  
Small Airways ◽  
Combined Immunodeficiency ◽  
Tissue Destruction ◽  
Primary Defect ◽  
Clear Cut ◽  
Lung Failure

Most cystic fibrosis (CF) patients die of lung failure, due to the combined effects of bacterial infection, neutrophil-mediated inflammation, and airway obstruction by hyperviscous mucus. To this day, it remains unclear where and how this pathological vicious circle is initiated in vivo. In particular, it has proven difficult to investigate whether inflammatory pathways are dysregulated in CF airways independently of infection. Also, the relative involvement of large (tracheobronchial) vs. small (bronchiolar) airways in CF pathophysiology is still unclear. To help address these issues, we used an in vivo model based on the maturation of human fetal CF and non-CF small airways in severe combined immunodeficiency mice. We show that uninfected mature CF small airway grafts, but not matched non-CF controls, undergo time-dependent neutrophil-mediated inflammation, leading to progressive lung tissue destruction. This model of mature human small airways provides the first clear-cut evidence that, in CF, inflammation may arise at least partly from a primary defect in the regulation of neutrophil recruitment, independently of infection.

IN VIVO TARGETING OF TIRC7, A NOVEL MEMBRANE PROTEIN, BY SPECIFIC ANTIBODY SIGNIFICANTLY PREVENTS SKIN ALLOGRAFT REJECTION

1999 ◽  
Vol 67 (7) ◽  
pp. S227
Author(s):  
N. Utku ◽  
M. Seifert ◽  
S. Fu ◽  
S. G. Tulius ◽  
T. Heinemann ◽  
...  
Keyword(s):  
Membrane Protein ◽  
Specific Antibody ◽  
Allograft Rejection ◽  
Skin Allograft

scholarly journals The cellular basis of allograft rejection in vivo. II. The nature of memory cells mediating second set heart graft rejection.

1978 ◽  
Vol 148 (4) ◽  
pp. 890-902 ◽  
Author(s):  
B M Hall ◽  
S Dorsch ◽  
B Roser
Keyword(s):  
Graft Rejection ◽  
Allograft Rejection ◽  
Lymphoid Tissue ◽  
Fold Increase ◽  
Transfer System ◽  
Memory Cells ◽  
Cellular Basis ◽  
Heart Graft ◽  
Histocompatibility Complex

An adoptive transfer system was used to study the cellular basis of memory in animals immunized by grafting with major histocompatibility complex incompatible tissue. Memory was characterised by a large (greater than 100 fold) increase in the potency of lymphocytes to precure graft rejection. This increase in potency endured for at least 1 yr after sensitization. The memory cells were shown to be Ig-- small lymphocytes which were long lived and which did not recirculate from blood to lymph in normal recipients although they did home to lymphoid tissue from which they could be recovered several months later. The thymus was not required either for the generation of memory cells or their maintenance. Cells carrying memory for alloantibody synthesis did recirculate normally but alloantibody synthesis was shown not to be required for rejection.

CELLULAR BASIS OF SKIN ALLOGRAFT REJECTION IN MICE

1998 ◽  
Vol 65 (6) ◽  
pp. 818-825 ◽  
Author(s):  
Naoki Yamamoto ◽  
Kuniko Einaga-Naito ◽  
Manabu Kuriyama ◽  
Yukimichi Kawada ◽  
Ryotaro Yoshida
Keyword(s):  
Allograft Rejection ◽  
Skin Allograft ◽  
Cellular Basis

THE CELLULAR BASIS OF ALLOGRAFT REJECTION IN VIVO

1983 ◽  
Vol 36 (6) ◽  
pp. 700-705 ◽  
Author(s):  
Bruce M. Hall ◽  
Ian de Saxe ◽  
Susan E. Dorsch
Keyword(s):  
Allograft Rejection ◽  
Cellular Basis

scholarly journals Phenotype, specificity, and function of T cell subsets and T cell interactions involved in skin allograft rejection.

1987 ◽  
Vol 165 (5) ◽  
pp. 1296-1315 ◽  
Author(s):  
A S Rosenberg ◽  
T Mizuochi ◽  
S O Sharrow ◽  
A Singer
Keyword(s):  
T Cells ◽  
T Cell ◽  
Allograft Rejection ◽  
T Cell Subsets ◽  
Skin Allograft ◽  
Th Cells ◽  
Effector Cells ◽  
T Effector Cells ◽  
Skin Allografts

In the present study we used an adoptive transfer model with athymic nude mice to characterize the T cells involved in initiating and mediating skin allograft rejection. It was found that skin allograft rejection in nude mice required the transfer of immunocompetent T cells and that such reconstitution did not itself stimulate the appearance of T cells derived from the nude host. Reconstitution with isolated populations of Lyt-2+/L3T4- T cells resulted in the rapid rejection of MHC class I-disparate skin allografts, whereas reconstitution with isolated populations of L3T4+/Lyt-2- T cells resulted in the rapid rejection of MHC class II-disparate and minor H-disparate skin allografts. By correlating these rejection responses with the functional capabilities of antigen-specific T cells contained within the reconstituting Lyt-2+ and L3T4+ T cell populations, it was noted that skin allografts were only rejected by mice that, as shown by in vitro assessment, contained both lymphokine-secreting Th cells and lymphokine-responsive Tk cells specific for the alloantigens of the graft. The ability of two such functionally distinct T cell subsets to interact in vivo to reject skin allografts was directly demonstrated in H-Y-specific rejection responses by taking advantage of the fact that H-Y-specific Th cells are L3T4+ while H-Y specific Tk cells are Lyt-2+. Finally, the importance of in vivo interactions between functionally distinct Th/T-inducer cells and T killer (Tk)/T-effector cells in skin allograft rejection was demonstrated by the observation that normal B6 mice retain Qala and Kbm6 skin allografts because of a selective deficiency in antigen-specific Th cells, even though they contain T-effector cells that, when activated, are able to reject such allografts. Thus, the ability to reject skin allografts is neither unique to a specialized subset of T cells with a given Lyt phenotype, nor unique to a specialized subset of helper-independent effector T cells with so-called dual function capability. Rather, skin allograft rejection can be mediated by in vivo collaborations between T-inducer cells and T-effector cells, and the two interacting T cell subsets can express different Lyt phenotypes as well as different antigen specificities.

CD25+CD4+ regulatory T cells generated by exposure to a model protein antigen prevent allograft rejection: antigen-specific reactivation in vivo is critical for bystander regulation

Blood ◽  
2005 ◽  
Vol 105 (12) ◽  
pp. 4871-4877 ◽  
Author(s):  
Mahzuz Karim ◽  
Gang Feng ◽  
Kathryn J. Wood ◽  
Andrew R. Bushell
Keyword(s):  
Adoptive Transfer ◽  
Allograft Rejection ◽  
Tolerance Induction ◽  
Treg Cells ◽  
Third Party ◽  
Antigen Specificity ◽  
Skin Allograft ◽  
Induction Strategy ◽  
Model Protein

Abstract The importance of CD25+CD4+ regulatory T (Treg) cells in the control of immune responses is established, but their antigen specificity in vivo remains unclear. Understanding Treg-cell specificity requirements will be important if their potential is to be developed for immunotherapy. Pretreatment of recipient mice with donor alloantigen plus anti-CD4 antibody generates CD25+CD4+ Treg cells with the capacity to prevent skin allograft rejection in adoptive transfer recipients. Here we demonstrate that, although this regulation can be antigen-specific, reactivation with the original tolerizing alloantigen allows the Treg cells to suppress rejection of third-party allografts. Aware of the limitations of alloantigen pretreatment, we asked whether graft-protective Treg cells could be generated against unrelated, nongraft antigens. We demonstrate that bystander regulation also extends to CD25+CD4+ Treg cells generated in vivo by exposure to nominal antigens under anti-CD4 antibody cover. Providing these Treg cells are reexposed to the tolerizing antigens before adoptive transfer, they prevent the rejection of fully allogeneic skin grafts. That this might form the basis of a clinically relevant tolerance induction strategy is demonstrated by the fact that, when combined with subtherapeutic anti-CD8 antibody, Treg cells generated in response to nongraft antigens facilitate the acceptance of cardiac allografts in primary recipients. (Blood. 2005;105:4871-4877)

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