Yu et al. (46) used mice deficient for both T - bet and RORγt as
T cell donors and showed that blockade of both Th1 and Th17 differentiation is required to prevent acute GVHD.
Not exact matches
Potential
donors must also have blood drawn to test for HIV, HTLV (human
T -
cell lymphotropic virus), Syphilis, Hepatitis B, and Hepatitis C.
To estimate the prevalence of positive serology among potential
donors to a human milk bank.Retrospective review of our experience with
donor serological testing at our milk bank over a 6 - year interval.Not - for - profit, regional human milk bank.Volunteer, unpaid potential
donors of human milk.Serological testing for syphilis, HIV, hepatitis B, hepatitis C, human
T cell lymphotropic virus type 1 (HTLV - 1) and human
T cell lymphotropic virus type 2 (HTLV - 2).
Donors should be tested for HIV 1 and 2, Human
T -
cell lymphotropic virus or HTLV 1 and 2, syphilis, and hepatitis B and C.
Nearly half of 13 blood
donors also had
T cells that seek and destroy
cells that make S. aureus Cas9 protein.
Now, by harnessing advances in genome editing to slice and dice genes in
donor T cells, researchers have created a new type of cancer immunotherapy.
Through adoptive transfer, these mice then received
donor T cells that had not been exposed to ovalbumin and therefore did not recognize it as a tolerable antigen.
When spleen CD4 +
T -
cells were transferred from heart - attack
donor mice to naïve recipient mice, they induced long - term left ventricle dysfunction, fibrosis and enlargement, hallmarks of heart failure.
One was a bone marrow transplant, in which imported
donor cells could manufacture healthy
T cells to fight invading germs.
The idea was to see if those naive
donor T cells would receive antigen - specific training from their pAPCs and then become tolerant to ovalbumin.
«We studied human
T cells, isolated from blood
donors of all ages, to compare mature cytotoxic
T cells with naive ones,» said Philip Ansumana Hull, graduate student in Ott's lab and one of the first authors of the study.
Memory
T cells against NS1 or E proteins were poorly cross-reactive, even in
donors preexposed to DENV.
Simultaneous
T cell antigen receptor (TCR) analysis in single
cells and bulk subsets revealed that CD4 - TEMRA
cells show marked clonal expansion compared with TCM and TEM
cells and that most of CD4 - TEMRA were dengue virus (DENV)-- specific in
donors with previous DENV infection.
Effector
T cells incite GvHD when they become overactive as the patient's immune system starts to rebuild itself from the
donor stem
cells.
A series of biological analyses of the mice with Tim - 1 and immune
cells isolated from human
donors showed that Ebola virus directly binds to
T -
cells through Tim - 1 protein binding and causes massive inflammation that thwarts the immune system.
While the
T cells of the liver transplant recipients reacted to the
donor organ
cells weakly, their reaction to other antigens was preserved.
Another approach to taming the
donor graft relies on a mixture of anti —
T cell anti-bodies called antithymocyte globulin, which is produced in horses or rabbits.
Given to the patient shortly before the transplant, the infusion of antibodies theoretically reduces the host's residual
T cells, minimizing the risk of graft rejection while eliminating
T cells from the
donor to thwart GVHD.
In the current study Davis's group used this approach to determine the frequency of H - Y — specific
T cells in a group of blood
donors.
The researchers inject
cells from the
donor, so that
T cells in the thymus are exposed to
donor cells as well as «self»
cells.
T cells normally attack tissue they do not recognise as «self,» causing organs which have been transplanted from other
donors to be rejected.
That approach, which shuts down the hyperactive
donor T cells when they first arrive, has not only allowed patients to tolerate grafts from increasingly mismatched hosts but, in several recent studies, has also cut rates of severe acute and chronic GVHD to less than 15 %.
Using a new method, the scientists therefore isolated
T cells specifically programmed to target the CMV virus from the blood of the
donor and transferred small numbers of these
cells to the patients.
In further investigations of human liver
cells from nearly 50
donor tissues of humans with varying degrees of body mass index (BMI) and liver fat, higher levels of CD8 +
T cells were linked with higher levels of blood sugar or more advanced fatty liver disease.
To determine whether ZFN - mediated disruption of cxcr4 indeed protects CD4 +
T cells from an in vitro HIV challenge, human CD4 +
T cells from three different ccr5 wild type
donors were stimulated and transduced with AdX4 - ZFNs or an AdR5 - ZFNs control.
If
T -
cells from a
donor are used, the
donor cells will view all of the patients»
cells as foreign and attack them.
The Great Ormond Street team was able to use
donor T -
cells to treat Layla because in addition to the CAR gene, they used gene editing to disable the gene for the protein that recognises other
cells as foreign, thereby preventing the
donor cells from attacking Layla's healthy
cells.
His team has used CRISPR gene editing to also disable the gene for the HLA proteins that mark a
donor T -
cell as foreign, reducing the chances of the recipient's immune system attacking the
donor cells.
Even so, in many cases there is yet another hurdle to overcome, because the patient's own immune system will see the
donor T -
cells as foreign and kill them.
By contrast, DN
T cells are able to mediate DTH to
donor alloantigens and induce apoptosis of
donor - specific corneal endothelial
cells.
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.
In our study, CD8 −
T cells from CD4 KO rejector mice failed to display CTL or DTH activity, yet they were capable of inducing
donor - specific apoptosis of corneal endothelial
cells.
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.
However, lymphocytes isolated from recipients of either CD8 +
T cells or CD8 −
T cells produced significant in vitro apoptosis of
donor - specific corneal endothelial
cells.
It occurs when the
donor T cells (the graft) don'
t recognize other
cells in the recipient's body (the host) and attacks them as if they are foreign bodies.
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.
Use of a lower dose of rabbit anti —
T - lymphocyte globulin (ATLG) was superior to a higher dose in children with hematologic malignancies undergoing allogeneic hematopoietic stem
cell transplantation (HSCT) from an unrelated
donor, according to the results of a study published in Lancet Oncology.
The program provides accurate, rapid genotyping and chimerism analysis; automatically identifies
donor and recipient peaks in post-BMT samples, calculates percent chimerism and quality metrics for single
donor or double
donor cases, easily appends for longitudinal monitoring post-BMT, and has multi-lineage capabilities for chimerism analysis of
T -
cells, B -
cells, and other
cell type populations.
GVHD is an immune - mediated disease in which
donor T cells recognize and attack the histocompatibility - disparate recipient; it involves multiple organs, such as the lung, liver, intestinal tract, and skin (2 — 4).
On day 0, recipient mice were transplanted with 5 × 106
T cell — depleted bone marrow (TCD - BM)
cells and 1 × 106 spleen
T cells from B6
donors.
In addition, we observed that
donor T cells recovered from VPA - treated BMT recipients and controls on day 14 showed comparable cytolytic activity against host - type leukemia
cells (Fig. 5F).
In addition, studies showed that the elimination of residual leukemia was primarily mediated by
donor CD8 + cytotoxic
T lymphocytes and NK
cells, whereas the inflammatory cytokines that are secreted mainly by CD4 + Th
cells have a very limited role in leukemia eradication but contribute significantly to the toxicity of GVHD (55).
University of Texas M.D. Anderson Cancer Center Tumor - specific alloantigen - anergic
donor - derived
T -
cell therapy after hematopoietic stem -
cell transplantation
Donor - type CD4 (+) CD25 (+) regulatory
T cells suppress lethal acute graft - versus - host disease after allogeneic bone marrow transplantation.
(A)
Donor - derived spleen
T cells from VPA recipients and control mice on days 7, 14, and 28 were stained for Foxp3 expression.
We then treated BMT recipients with VPA or vehicle and recovered
donor T cells from spleen and MLN of recipients on the indicated days after transplantation.
(F)
Donor T cells were isolated from recipient spleen on day 14 for CTL assay against leukemia
cells.
(B) Representative percentage of
donor - derived spleen
T cells expressing Foxp3 on days 7, 14, and 28.
(C and D) Flow cytometry analysis of intracellular IFN - γ and IL - 17A on
donor - derived CD4 +
T cells from spleen of control mice and VPA recipients on the indicated days.
These findings reveal a unique role for VPA as a histone deacetylase inhibitor in reducing the
donor CD4 +
T cells that contribute to GVHD, which may provide a strategy to reduce GVHD while preserving the GVL effect.