Host thymectomy and cyclosporine lead to unstable skin graft tolerance after class I mismatched allogeneic neonatal thymic transplantation in mice

2005 ◽  
Vol 15 (1) ◽  
pp. 25-33 ◽  
Author(s):  
José-Ignacio Rodríguez-Barbosa ◽  
Gary W. Haller ◽  
Guiling Zhao ◽  
David H. Sachs ◽  
Megan Sykes
1987 ◽  
Vol 166 (4) ◽  
pp. 982-990 ◽  
Author(s):  
T Ichikawa ◽  
E Nakayama ◽  
A Uenaka ◽  
M Monden ◽  
T Mori

The cellular mechanisms of skin graft rejection with allelic H-2 class I differences were studied by examining the effect on graft survival of in vivo administration of anti-Lyt-2.2 mAb, anti-L3T4 mAb, or both to recipient mice. The injections of anti-Lyt-2.2 mAb and anti-L3T4 mAb caused selective depletions of Lyt-2+ cells and L3T4+ cells, respectively. Injection of anti-Lyt-2.2 mAb significantly prolonged graft survival in 7 of 12 combinations of H-2D-end difference, but did not prolong graft survival in 5 other combinations of H-2D-end difference, or in 2 combinations of H-2K-end difference. Injection of anti-L3T4 mAb did not prolong graft survival in any combinations with class I difference tested. Injection of anti-L3T4 mAb plus anti-Lyt-2.2 mAb markedly prolonged graft survival in the combinations with class I difference in which anti-Lyt-2.2 mAb had no effect and overcame the effect of anti-Lyt-2.2 mAb in those in which anti-Lyt-2.2 mAb had an effect in prolonging graft survival. These results indicated that in combinations in which anti-Lyt-2.2 mAb did not prolong graft survival, class I antigen stimulated L3T4+ effector cells when Lyt-2+ cells were blocked and Lyt-2+ effector cells when L3T4+ cells were blocked. On the other hand, in the combinations in which anti-Lyt-2.2 mAb prolong graft survival, these antigens initially caused preferential stimulation of Lyt-2+ but not L3T4+ effector cells, although delayed activation of L3T4+ effector cells occurred when Lyt-2+ cells were blocked. Furthermore, a significant correlation was found between the effect of anti-Lyt-2.2 mAb in prolonging graft survival and the failure of recipient mice to produce H-2 antibody. These results can be taken as evidence that L3T4+ effector cells are not involved in the initial phase of graft rejection in these combinations.


2003 ◽  
Vol 11 (1) ◽  
pp. 23-29 ◽  
Author(s):  
Julie A. Margenthaler ◽  
Keith Landeros ◽  
Masaaki Kataoka ◽  
M.Wayne Flye

2017 ◽  
Vol 181 ◽  
pp. 83-95.e3 ◽  
Author(s):  
Maria-Luisa del Rio ◽  
Ana Maria Bravo Moral ◽  
Carlos Fernandez-Renedo ◽  
Leo Buhler ◽  
Jose-Antonio Perez-Simon ◽  
...  

1999 ◽  
Vol 67 (7) ◽  
pp. S259
Author(s):  
A. Wu ◽  
K. Yamada ◽  
M. Awwad ◽  
A. Shimizu ◽  
A. Watts ◽  
...  

1991 ◽  
Vol 173 (1) ◽  
pp. 261-264 ◽  
Author(s):  
M Kawai ◽  
Y Obata ◽  
N Hamasima ◽  
T Takahashi ◽  
A Uenaka ◽  
...  

Differential involvement of CD4+ cells in mediating class I-disparate skin graft rejection was investigated using quantitatively different Kb transgenic mice as donors under conditions in which CD8+ cells were blocked in vivo by administration of anti-CD8 monoclonal antibody (mAb). Tg.H-2Kb-1 and -2 are C3H transgenic mice with 14 and 4 copies, respectively, of the H-2Kb gene. Cell surface expression of Kb antigen and the Kb antigenicity of skin for eliciting graft rejection with homozygous and heterozygous transgenic mice were correlated with the copy number. In vivo administration of anti-Lyt-2.1 (CD8) mAb markedly prolonged survival of heterozygous and homozygous C3H Tg.H-2Kb-2 skin grafted onto C3H mice, but prolonged survival of heterozygous Tg.H-2Kb-1 skin grafts much less and did not prolong survival of homozygous Tg.H-2Kb-1 grafts. Administration of anti-L3T4 (CD4) mAb alone did not have any effect on skin graft rejection. Administration of anti-L3T4 (CD4) mAb with anti-Lyt-2.1 (CD8) mAb blocked rejection in all combinations. These findings indicate that a quantitative difference of class I antigen caused differential activation of CD4+ cells under conditions in which CD8+ cells were blocked.


2019 ◽  
Vol 20 (9) ◽  
pp. 2056 ◽  
Author(s):  
Frederik Schlottmann ◽  
Sarah Strauss ◽  
Kevin Hake ◽  
Peter M. Vogt ◽  
Vesna Bucan

Skin transplantation, especially in burn patients, is still challenging because surgeons are faced with limited disposability of autologous donor side material. The in vitro culture of keratinocytes has become an important reconstructive option. However, only non-immunogenic allogenic keratinocytes offer the opportunity to develop a skin graft that can overcome rejection. The purpose of the study was to develop targeted gene modification of keratinocytes in order to reduce immunogenicity for the use as allogenic transplantable skin graft by decreasing the expression of MHC class I. To reduce MHC class I expression, viral vectors containing the US11 gene of human cytomegalovirus were generated and tested on their functionality using Western blotting, indirect immunofluorescence staining, and flow cytometry. Transfected keratinocytes were seeded on commercially available bovine collagen-elastin matrices and further cultured for histological and cell survival assays. Results showed transient down-regulation of MHC class I after 24 h post-transfection, with recovery of MHC class I expression after 48 h. Histological assessments showed long-term cell survival as well as histological patterns comparable to epidermal layers of healthy human skin. The data postulates the potential application of US11 transfected keratinocytes as an approach towards an immune-privileged skin substitute. Nevertheless, further studies and data are needed.


2020 ◽  
Vol 104 (S3) ◽  
pp. S97-S98
Author(s):  
Mario Leong ◽  
Moumita Paul-Heng ◽  
Eric T. Son ◽  
Markus J. Hofer ◽  
Chuanmin Wang ◽  
...  

Author(s):  
T. A. Stewart ◽  
D. Liggitt ◽  
S. Pitts ◽  
L. Martin ◽  
M. Siegel ◽  
...  

Insulin-dependant (Type I) diabetes mellitus (IDDM) is a metabolic disorder resulting from the lack of endogenous insulin secretion. The disease is thought to result from the autoimmune mediated destruction of the insulin producing ß cells within the islets of Langerhans. The disease process is probably triggered by environmental agents, e.g. virus or chemical toxins on a background of genetic susceptibility associated with particular alleles within the major histocompatiblity complex (MHC). The relation between IDDM and the MHC locus has been reinforced by the demonstration of both class I and class II MHC proteins on the surface of ß cells from newly diagnosed patients as well as mounting evidence that IDDM has an autoimmune pathogenesis. In 1984, a series of observations were used to advance a hypothesis, in which it was suggested that aberrant expression of class II MHC molecules, perhaps induced by gamma-interferon (IFN γ) could present self antigens and initiate an autoimmune disease. We have tested some aspects of this model and demonstrated that expression of IFN γ by pancreatic ß cells can initiate an inflammatory destruction of both the islets and pancreas and does lead to IDDM.


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