To study infiltration
of allografts, frozen sections were stained with peroxidase - conjugated antibodies against either CD4 or CD8 as recommended by the manufacturer (BD Biosciences, San Diego, CA).
To determine the histology
of the allografts, we sacrificed our transplanted animals on either day 40 or day 100 post-transplantation.
Reconstitution with syngeneic plus allogeneic or xenogeneic bone marrow leads to specific acceptance
of allografts or xenografts.
Allospecific CTL and DTH responses have been associated with the immune rejection of various categories
of allografts.
This study was also of only one type
of allograft (Tibialis Posterior).
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.
APOL1 genetic testing can help you make informed decisions about how to manage future risks
of allograft failure in your renal transplant patients.
To determine a possible impact
of the allograft on mixed chimerism, we measured the levels of bone marrow mixed chimerism 40 days post cardiac graft transplantation.
This preparation provides access to the patient's own stem cells, which may undergo osteogenic differentiation in response to delivery
of the allograft BMDMSC.
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).
Correlation
of leukocyte groups with skin and renal
allograft survival indicates that ranks
of histocompatibility based upon current genetic concepts
of the HL - A system may provide an approach to the selection
of optimally compatible subjects for clinical organ transplantation.
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.
Such
allografts have already been performed: a portion
of respective tissue is being recovered from a dead donor and placed under the mucosa
of the recipient's stomach.
«Long - term prevention
of organ rejection: Biologists use immunoproteasome inhibition to prevent chronic antibody - mediated
allograft rejection.»
Several mTOR inhibitors have already been approved for therapeutic use, in particular in the treatment
of cancer and
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).
BALB / c corneal
allografts were transplanted 24 hr later and the fate
of the corneal
allografts determined.
Interestingly, recipients
of CD8 + T lymphocytes failed to mount DTH responses to BALB / c alloantigens (Figure 4), even though similar panels
of mice rejected 95 %
of their BALB / c corneal
allografts (Figure 2B).
Immunohistochemical staining
of rejected human corneal
allografts has revealed the presence
of apoptosis in corneal stromal cells (5).
The capacity
of CD8 − T cells from CD4 KO donors to mediate corneal
allograft rejection is puzzling and on the surface, counterintuitive, since these cells are presumably double negative (DN) T cells.
Either
of these effector mechanisms might contribute to corneal
allograft rejection.
An adoptive transfer experiment was performed to confirm that the high incidence
of corneal
allograft rejection was immune - mediated.
By contrast, 71 % (5/7)
of the beige nude mice that received spleen cells from CD4 KO mice rejected their BALB / c corneal
allografts.
Removing one immune effector element only reveals the presence
of an ancillary pathway for
allograft rejection.
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).
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.
T lymphocytes are required for the rejection
of corneal
allografts, as athymic, T cell - deficient nude mice do not reject corneal
allografts (3).
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.
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).
Several studies suggest that a significant number
of corneal
allografts undergo rejection in the absence
of CD4 + T cells.
CD8 + and CD8 − T cells were collected from either C57BL / 6 mice or adoptive cell transfer recipients one week after the rejection
of BALB / c corneal
allografts.
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.
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).
By contrast, adoptive transfer
of CD8 − spleens cells from similar donors resulted in the rejection
of corneal
allografts in almost half
of the hosts.
However, some studies have demonstrated a role for CD8 + T cell - mediated rejection
of skin and cardiac
allografts (16, 17).
Additional adoptive transfer experiments were performed to ascertain the role
of CD8 + and CD8 − T lymphocytes in CD4 - independent rejection
of corneal
allografts.
None
of the ten C57BL / 6 beige nude mice rejected BALB / c corneal
allografts (Figure 2A).
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.
This study examined the role
of CD4 + T cell - independent mechanisms
of corneal
allograft rejection.
Development
of DTH responses to donor alloantigens has been correlated with corneal
allograft rejection.