Role of the thymus in heterotopic cardiac allograft survival in miniature swine: evidence for the need of thymic emigrants immediately post-transplantation, and thymic immigrants for long term tolerance induction

2003 ◽  
Vol 22 (1) ◽  
pp. S162
Author(s):  
S Yamamoto ◽  
P.A Vagefi ◽  
J.D Mezrich ◽  
S.L Houser ◽  
C Kamano ◽  
...  
2001 ◽  
Vol 356 (1409) ◽  
pp. 727-738 ◽  
Author(s):  
Karl L. Womer ◽  
Richard S. Lee ◽  
Joren C. Madsen ◽  
Mohamed H. Sayegh

The most common cause of chronic allograft loss is an incompletely understood clinicopathological entity called chronic rejection (CR). Recent reports suggest an improvement in long–term renal allograft survival, although it is not clear from these data whether a true reduction of biopsy–proven CR has occurred. Although newer immunosuppressive medications have greatly reduced the incidence of acute rejection (AR) in the early post–transplantation period, the ideal therapy for both AR and CR would be to achieve a state of tolerance. By definition, such a state should allow for indefinite allograft survival, with no histopathological evidence of CR, despite immunocompetence in the host (i.e. without the need for chronic immunosuppression). Although several experimental studies are able to achieve tolerance, with clear improvement in allograft survival, detailed studies on graft function and morphology are often not included. This review will discuss possible ways that tolerance induction could lead to a CR–free state. General mechanisms of CR and transplantation tolerance induction are discussed as well as the difficulties in translating small animals studies into large animals and humans.


1998 ◽  
Vol 9 (5) ◽  
pp. 891-898
Author(s):  
M Schaub ◽  
T H Stadlbauer ◽  
A Chandraker ◽  
J P Vella ◽  
L A Turka ◽  
...  

Blocking CD28-B7 T cell costimulatory activation by the fusion protein CTLA4Ig prevents rejection and induces long-term graft acceptance in various experimental transplant models. There are reported differences in the efficacy of CTLA4Ig in renal and cardiac rodent allograft models, but it is not clear whether these are due to the strain or species differences investigated in the different studies reported. This study investigates the effect of blocking CD28-B7 T cell costimulation with murine CTLA4Ig in rat models of acute renal and cardiac allograft rejection models, using the same complete major histocompatibility complex-incompatible strain combination. A single injection of murine CTLA4Ig 2 d after engraftment was able to induce long-term graft acceptance (> 100 d) in 54% of Lewis rat recipients of Wistar-Furth kidneys. Transferring this protocol into the acute Wistar-Furth to Lewis heart allograft model resulted in a mean graft survival time of 24.7+/-16.9 d, and all grafts were ultimately rejected. Only concomitant injection of donor cells (4 x 10(7) splenocytes) plus a single injection of CTLA4Ig on the day of transplant could induce long-term graft acceptance in 50% of animals. In both the cardiac and renal transplant models, the thymus and spleen were required for induction of tolerance. The maintenance phase of tolerance, however, did not require an intact thymus but did require the presence of a spleen. These data have important clinical applicability because human studies with T cell costimulatory blockade are being planned.


2020 ◽  
Vol 35 (8) ◽  
pp. 1855-1863 ◽  
Author(s):  
Stina Järvholm ◽  
Anders Enskog ◽  
Catrina Hammarling ◽  
Pernilla Dahm-Kähler ◽  
Mats Brännström

Abstract STUDY QUESTION How is a women’s self-image affected by uterus transplantation (UTx)? SUMMARY ANSWER Women experienced receiving a uterus in both positive and negative ways, but in general, their self-image was positively affected; regardless of whether they have given birth to a child or not, recipients describe themselves as being ‘back to normal’ after the hysterectomy to remove the transplanted uterus. WHAT IS KNOWN ALREADY UTx has repeatedly proved to be a successful treatment for absolute uterine factor infertility. However, there has been no previous qualitative long-term research into the self-image of women undergoing UTx. STUDY DESIGN, SIZE, DURATION This complete, prospective cohort study included the nine recipients of the first UTxs performed in Sweden mostly in 2013. Interviews took place in the 5 years following surgery. PARTICIPANTS/MATERIALS, SETTING, METHODS Eight out of the nine recipients had congenital absence of the uterus, a characteristic of Mayer–Rokitansky–Küster–Hauser syndrome, and one recipient lacked a uterus after a radical hysterectomy due to cervical cancer. The mean age of participants was 31.5 years at inclusion and at this time they all lived in stable marital relationships. Post-transplantation, interviews were performed annually for 5 years, comprising a total of 43 interviews. The interview followed a semi-structured guide. All interviews (median duration of around 25 minutes) were recorded, transcribed verbatim and then analysed by thematic approach. MAIN RESULTS AND THE ROLE OF CHANCE The joys and frustrations of becoming a ‘complete’ woman are seen as a master theme, which influences the three underlying subthemes, a changed self-perception, a changed body and a changed sexuality. Each of these subthemes have three underlying categories. LIMITATIONS, REASONS FOR CAUTION The small sample size is a limitation. WIDER IMPLICATIONS OF THE FINDINGS The results provide information that will be helpful in pre-operative screening procedures and in the psychological support offered both to women who experienced successful and unsuccessful outcomes following UTx. STUDY FUNDING/COMPETING INTEREST(S) Funding was received from the Jane and Dan Olsson Foundation for Science; the Knut and Alice Wallenberg Foundation; an ALF grant from the Swedish state under an agreement between the government and the county councils; the Swedish Research Council; a Ferring Pharmaceuticals scholarship in memory of Robert Edwards; and the Iris Jonzén-Sandblom and Greta Jonzén Foundation. The authors have no competing interests. TRIAL REGISTRATION NUMBER NCT01844362.


2019 ◽  
Vol 116 (27) ◽  
pp. 13508-13516 ◽  
Author(s):  
Nina Pilat ◽  
Mario Wiletel ◽  
Anna M. Weijler ◽  
Romy Steiner ◽  
Benedikt Mahr ◽  
...  

Injection of Interleukin-2 (IL-2) complexed with a particular anti–IL-2 monoclonal antibody (mab) JES6-1 has been shown to selectively expand CD4+Foxp3+ T regulatory T cells (Tregs) in vivo. Although the potency of this approach with regard to transplantation has already been proven in an islet transplantation model, skin graft survival could not be prolonged. Since the latter is relevant to human allograft survival, we sought to improve the efficiency of IL-2 complex (cplx) treatment for skin allograft survival in a stringent murine skin graft model. Here, we show that combining low doses of IL-2 cplxs with rapamycin and blockade of the inflammatory cytokine IL-6 leads to long-term (>75 d) survival of major histocompatibility complex-different skin allografts without the need for immunosuppression. Allograft survival was critically dependent on CD25+FoxP3+ Tregs and was not accompanied by impaired responsiveness toward donor alloantigens in vitro after IL-2 cplx treatment was stopped. Furthermore, second donor-type skin grafts were rejected and provoked rejection of the primary graft, suggesting that operational tolerance is not systemic but restricted to the graft. These findings plus the lack of donor-specific antibody formation imply that prolonged graft survival was largely a reflection of immunological ignorance. The results may represent a potentially clinically translatable strategy for the development of protocols for tolerance induction.


Allergy ◽  
2006 ◽  
Vol 61 (2) ◽  
pp. 173-180 ◽  
Author(s):  
B. Winkler ◽  
K. Hufnagl ◽  
A. Spittler ◽  
M. Ploder ◽  
E. Kallay ◽  
...  

2014 ◽  
Vol 14 (9) ◽  
pp. 2001-2010 ◽  
Author(s):  
J. R. Scalea ◽  
M. Okumi ◽  
V. Villani ◽  
A. Shimizu ◽  
H. Nishimura ◽  
...  

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