Balb / c third - party allografts were acutely rejected in chimeric animals, as were control MRL
allografts in non-chimeric animals.
Allogenic
allografts in chimeric mice were harvested on either day 40 or day 100 - post transplantation.
Studies in CD8 knockout (KO) and perforin KO mice demonstrated that CD8 + cytotoxic T lymphocytes (CTL) are unnecessary for the rejection of corneal
allografts in mice (8, 9).
By contrast, adoptive transfer of CD8 − spleens cells from similar donors resulted in the rejection of corneal
allografts in almost half of the hosts.
Histopathological examination of rejected corneal
allografts in CD4 KO mice revealed a mixed inflammatory infiltrate containing large numbers of neutrophils and mononuclear cells, which was indistinguishable from the infiltrate seen in rejected corneal
allografts in wild - type mice (data not shown).
The present demonstration of T cell - mediated apoptosis of allogeneic corneal cells from CD4 KO mice is consistent with previous findings, which noted the presence of apoptotic keratocytes and corneal endothelial cells in rejected corneal
allografts in humans and rats respectively (5, 32).
«The use of 15 - mg / kg ATLG was associated with statistically improved event - free survival in the subgroups of children with acute leukemia or with acute lymphoblastic leukemia, which represents the more frequent indication for
an allograft in hematologic malignancies of childhood.»
Fresh hypothermically stored amniotic
allograft in the treatment of chronic nonhealing ulcers: a prospective case series - Dove Medical Press
Initial Experience with Tricortical Iliac Crest Bone Graft and Human Amniotic
Allograft in Evans Calcaneal Osteotomy
Not exact matches
A study
in 2011 looking at more than 645 ACL surgeries found that
in patients between the ages of 10 ««19,
allograft tissue had a four times higher failure rate than using your own tissue.
This may entail making small holes
in the bone to allow new cartilage to grow (microfracture), taking cartilage from another part of the athlete's knee and transplanting it into the defect (osteochondral autograft transfer), taking cartilage cells from the knee and then having them grown
in a lab for later re-implantation (autologous chondrocyte implantation), or taking cartilage from a person who has passed away and placing it
in the defect (osteochondral
allograft transfer).
The study, «Optimizing Femoral - head Osteochondral
Allograft Transplantation
in a Preclinical Model,» recently was published
in the Journal of Orthopaedic Translation.
The rate of early
allograft dysfunction — a serious and potentially deadly complication of transplantation — occurred
in only 10 % of machine - stored liver recipients, versus 30 % of those allocated ice - stored ones.
Using an approach developed at Maisonneuve - Rosemont, consisting of an autograft to reduce tumour mass followed by a family
allograft three to four months later to clean the bone marrow of myeloma cells with immune cells from a family donor (immunotherapy), the study resulted
in a total cure rate of 41 %, a record level using this strategy.
Moreover, patients
in complete remission six months after the
allograft had a relapse - free survival rate of 60 %.
Overall, the autograft strategy followed by
allograft resulted
in relapse - free survival rates of 20 - 25 %
in the long term.
Moreover,
in the same study, the mortality rate associated with this treatment over ten years was 10 %, an extremely low rate following a family donor
allograft.
«Our study results highlight that
in a young athletic population,
allografts (tissue harvested from a donor) fail more frequently than using autografts (tissue harvested from the patient),» said Craig R. Bottoni, MD, lead author from Tripler Army Medical Center
in Honolulu, Hawaii.
Several mTOR inhibitors have already been approved for therapeutic use,
in particular
in the treatment of cancer and
allograft rejection.
Tissue - cultured corneal cells were used for
in vitro studies rather than the usual lymphoid cells since corneal cells are the relevant target cells
in vivo during corneal
allograft rejection.
In the present study we sought to determine the role and mechanisms of CD4 - independent rejection of corneal
allografts.
However, closer scrutiny of these studies raises questions about the role of CD4 + T cells as the sole mediators of corneal graft rejection, as corneal
allografts undergo immune rejection
in 33 % of the mice and 64 % of the rats treated with anti-CD4 monoclonal antibody (12, 13) and
in 45 % of the CD4 KO mice (14).
Immunohistochemical staining of rejected human corneal
allografts has revealed the presence of apoptosis
in corneal stromal cells (5).
BALB / c corneal
allografts underwent rejection
in 46 % (6/13; MST = 46 days) of the recipients of CD8 − T lymphocytes and
in 95 % (19/20; MST = 15 days) of the recipients of CD8 + T lymphocytes (Figure 2B).
The results of a typical experiment are shown
in Figure 3 and demonstrate that even though spleen cells from CD4 KO mice could adoptively transfer corneal
allograft rejection, they did not display conventional CTL activity against either BALB / c corneal epithelial or endothelial cells.
Although the immune basis for corneal
allograft rejection was formally established
in experimental animals by Maumenee (33) over 50 years ago, the exact immune mechanisms that lead to the corneal graft failure remain poorly understood.
The present findings are derived from studies using CD4KO mice and thus, raise the question as to whether the CD4 + T cell - independent immune mechanisms
in CD4 KO mice differ from those involved
in corneal
allograft rejection
in wild - type mice whose CD4 + T cells population have been depleted with monoclonal antibodies.
The role of DN T cells
in corneal
allograft rejection was confirmed
in two separate
in vitro assays
in which CD8 − cells were isolated from CD4 KO donors that had rejected corneal
allografts and were found to induce apoptosis of donor - specific corneal cells.
The combination of anti-NKG2D and CTLA - 4 Ig therapy prolongs islet
allograft survival
in a murine model.
Indeed, our results indicate that adoptive transfer of CD8 + T cells from CD4 KO mice that had rejected corneal
allografts resulted
in the rejection of 95 % of the corneal
allografts transplanted to athymic recipients.
The capacity of CD8 + T cells to mediate corneal
allograft rejection could have been due to the CTL population that might have been present
in the CD8 + T cell suspensions used
in the adoptive transfer inocula.
Several studies suggest that a significant number of corneal
allografts undergo rejection
in the absence of CD4 + T cells.
However,
in vitro assays using spleen cells from CD4 KO mice that had rejected BALB / c corneal
allografts failed to detect CTL activity against donor corneal epithelial or endothelial cells.
Current projects are investigating: 1) the expression of inflammatory genes during ischemia and reperfusion of kidneys during urology transplantation and
in mouse models; 2) the expression of inflammatory genes and proteins
in urine as markers indicating the presence of rejection
in renal
allografts; and 3) the role of adhesion molecules and chemokines
in directing leukocyte infiltration into organ
allografts.
In their study, DN T cells displayed allospecific cytotoxicity in vitro and mediated tumor allograft rejection in viv
In their study, DN T cells displayed allospecific cytotoxicity
in vitro and mediated tumor allograft rejection in viv
in vitro and mediated tumor
allograft rejection
in viv
in vivo.
Overall, MSCs can exert protective effects
in ischemic reperfusion injuries through anti-inflammatory and paracrine factors and this likely plays an important part
in MSC enhancement of
allograft survival.
The results indicated that 54 % (38/70) of the BALB / c corneal
allografts underwent rejection
in the CD4 KO hosts, while 100 % of the grafts were rejected
in wild - type C57BL / 6 mice (Figure 1).
Additional adoptive transfer experiments were performed to ascertain the role of CD8 + and CD8 − T lymphocytes
in CD4 - independent rejection of corneal
allografts.
Insufficient or excess complement activation has been shown to be important
in a wide range of disease states, such as multiple sclerosis, myasthenia gravis, systemic lupus erythematosus, rheumatoid arthritis, and age - related macular degeneration, as well as
in allograft rejection.
The results reported here reaffirm previous findings indicating that T cells are absolutely required for corneal
allograft rejection
in the mouse (3).
These findings also demonstrate the remarkable plasticity and redundancy
in the immune mechanisms that mediate
allograft rejection.
Spleen cells were isolated 7 — 14 days after C57BL / 6 CD4 KO mice had rejected BALB / c corneal
allografts and were tested for anti - BALB / c CTL
in a conventional 4 - hr 51Cr - release assay using BALB / c corneal epithelial and endothelial target cells.
Until recently, the dogma
in transplantation immunology held that
allograft rejection was a Th1 CD4 + cell - mediated process.
Experiments were performed to confirm that a significant number of corneal
allografts underwent rejection
in the absence of CD4 + T cells.
They found out that pre-organ transplant infusion of MSC
in 1 or 2 doses [on day - 7 and day - 1] induced a profound T cell hyporesponsiveness and prolonged B6C3 cardiac
allograft survival.
Hepatocyte growth factor prevents the development of chronic
allograft nephropathy
in rats.
Interestingly, Azuma et al 167 showed that HGF treatment prevents chronic
allograft nephropathy
in rats.
Ge W et al 40 reported that MSCs could induce kidney
allograft tolerance by inducing the generation of CD4 + CD25 + FoxP3 + Tregs
in vivo.
We have also generated T - regs (CD4 + / 25high / 127low / --RRB-
in vitro from donor AD - MSC and recipient peripheral blood mononuclear cells and these T - regs are infused
in thymus of renal
allograft recipients after kidney transplantation.
In addition, infusion of recipient - derived B6 MSC tolerized a semiallogeneic B6C3 cardiac
allograft, but not a fully MHC - mismatched BALB / c graft, and expanded Treg.